Splice variants associated with neomorphic SF3B1 mutants

ABSTRACT

Splice variants associated with neomorphic SF3B1 mutations are described herein. This application also relates to methods of detecting the described splice variants, and uses for diagnosing cancer, evaluating modulators of SF3B1, and methods of treating cancer associated with mutations in SF3B1.

The present application is a national stage application under 35 U.S.C.§ 371 of international application number PCT/US2016/049490, filed Aug.30, 2016, which designated the U.S. and claims the benefit of priorityto U.S. Provisional Patent Application No. 62/212,876, filed Sep. 1,2015, the contents of which are hereby incorporated by reference hereinin their entirety.

The instant application contains a Sequence Listing which has beensubmitted electronically in ASCII format and is hereby incorporated byreference in its entirety. The ASCII copy, created on May 16, 2014, isnamed 12636.6-304_SL.txt and is 183 kilobytes in size.

RNA splicing, a highly regulated molecular event orchestrated by thespliceosome, results in the removal of intronic sequences from pre-mRNAto generate mature mRNA. Dysregulation of RNA splicing has beenidentified as a causative defect in several diseases. In addition,dysregulated splicing has been proposed to play an important role intumorigenesis and resistance to therapy; however, the molecular causesof dysregulated splicing in cancer have remained elusive.

SF3B1 is a protein involved in RNA splicing. It forms part of the U2snRNP complex which binds to the pre-mRNA at a region containing thebranchpoint site and is involved in early recognition and stabilizationof the spliceosome at the 3′ splice site (3′ ss). A thorough andsystematic analysis of the effects of SF3B1 mutations is needed todefine their effects on RNA splicing in cells and may lead to noveltherapeutic approaches for SF3B1 mutant cancers.

The description provided herein demonstrates that certain SF3B1mutations result in neomorphic activity with the production of known andnovel splicing alterations. In addition, lineage-specific splicingaberrations were identified in chronic lymphocytic leukemia (CLL),melanoma, and breast cancer. Furthermore, treatment of SF3B1-mutantcancer cell lines, xenografts, and CLL patient samples with modulatorsof SF3B1 reduced aberrant splicing and induced tumor regression.

SUMMARY

The methods described herein involve detecting or quantifying theexpression of one or more splice variants in a cell containing aneomorphic mutant SF3B1 protein. Various embodiments of the inventioninclude detecting or quantifying splice variants to determine whether apatient has a cancer with one or more neomorphic SF3B1 mutations.Additional embodiments include measuring the amount of a splice variantto evaluate the effects of a compound on a mutant SF3B1 protein. Furtherembodiments include methods of treating a patient who has cancer cellswith a neomorphic mutant SF3B1 protein.

Various embodiments encompass a method of detecting one or more splicevariants selected from rows 1-790 of Table 1 in a biological sample,comprising:

a) providing a biological sample suspected of containing one or moresplice variants;

b) contacting the biological sample with one or more nucleic acid probescapable of specifically hybridizing to the one or more splice variants,and

c) detecting the binding of the one or more probes to the one or moresplice variants.

In some embodiments, the one or more nucleic acid probes capable ofspecifically hybridizing to the one or more splice variants eachcomprise a label. In some embodiments, the method of detecting one ormore splice variants selected from rows 1-790 of Table 1 in a biologicalsample further comprises contacting the biological sample with one ormore additional nucleic acid probes, wherein the additional probes areeach labeled with a molecular barcode.

Embodiments further encompass a method of modulating the activity of aneomorphic mutant SF3B1 protein in a target cell, comprising applying anSF3B1-modulating compound to the target cell, wherein the target cellhas been determined to express one or more aberrant splice variantsselected from rows 1-790 of Table 1 at a level that is increased ordecreased relative to the level in a cell not having the neomorphicmutant SF3B1 protein.

Embodiments also encompass a method for evaluating the ability of acompound to modulate the activity of a neomorphic mutant SF3B1 proteinin a target cell, comprising the steps of:

a) providing a target cell having a mutant SF3B1 protein;

b) applying the compound to the target cell; and

c) measuring the expression level of one or more splice variantsselected from row 1-790 of Table 1.

In some embodiments, the method for evaluating the ability of a compoundto modulate the activity of a neomorphic mutant SF3B1 protein in atarget cell further comprises the step of measuring the expression levelof one or more splice variants selected from row 1-790 of Table 1 beforestep (b).

In some embodiments, the neomorphic mutant SF3B1 protein is selectedfrom K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E,K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, orR625L. In some embodiments, the neomorphic mutant SF3B1 protein isselected from E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C,R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y,H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N,K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N,I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D,D781E, D781G, or D781N.

In some embodiments, the step of measuring the expression level of oneor more splice variants comprises using an assay to quantify nucleicacid selected from nucleic acid barcoding (e.g. NanoString®), RT-PCR,microarray, nucleic acid sequencing, nanoparticle probes (e.g.SmartFlare™), and in situ hybridization (e.g. RNAscope®).

In some embodiments, the step of measuring the expression level of oneor more splice variants comprises measuring the number of copies of theone or more splice variant RNAs in the target cell.

In further embodiments, the compound is selected from a small molecule,an antibody, an antisense molecule, an aptamer, an RNA molecule, and apeptide. In further embodiments, the small molecule is selected frompladienolide and a pladienolide analog. In additional embodiments, thepladienolide analog is selected from pladienolide B, pladienolide D,E7107, a compound of formula 1:

a compound of formula 2:

a compound of formula 3:

or a compound of formula 4:

In some embodiments, the target cell is obtained from a patientsuspected of having myelodysplastic syndrome, chronic lymphocyticleukemia, chronic myelomonocytic leukemia, or acute myeloid leukemia. Insome embodiments, the target cell is obtained from a sample selectedfrom blood or a blood fraction or is a cultured cell derived from a cellobtained from a sample chosen from blood or a blood fraction. In someembodiments, the target cell is a lymphocyte.

In further embodiments, the target cell is obtained from a solid tumor.In some embodiments, the target cell is a breast tissue cell, pancreaticcell, lung cell, or skin cell.

In some embodiments, one or more of the aberrant variants are selectedfrom rows 1, 7, 9, 10, 13, 15, 16, 18, 21, 24, 27, 28, 30, 31, 33, 34,48, 51, 62, 65, 66, 71, 72, 81, 84, 89, 91, 105, 107, 121, 135, 136,152, 178, 235, 240, 247, 265, 267, 272, 276, 279, 282, 283, 286, 292,295, 296, 298, 302, 306, 329, 330, 331, 343, 350, 355, 356, 360, 364,372, 378, 390, 391, 423, 424, 425, 426, 431, 433, 438, 439, 443, 445,447, 448, 451, 452, 458, 459, 460, 462, 468, 469, 472, 500, 508, 517,519, 521, 524, 525, 527, 528, 530, 533, 536, 540, 543, 548, 545, 554,556, 559, 571, 573, 580, 582, 583, 597, 601, 615, 617, 618, 639, 640,654, 657, 666, 670, 680, 727, 730, 750, 758, 767, or 774 of Table 1.

In some embodiments, one or more of the aberrant variants are selectedfrom rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545,548 or 566 of Table 1.

Embodiments further encompass a method for treating a patient with aneoplastic disorder, comprising administering a therapeuticallyeffective amount of an SF3B1-modulating compound to the patient, whereina cell from the patient has been determined to:

-   -   a) contain a neomorphic mutant SF3B1 protein; and    -   b) express one or more aberrant splice variants selected from        rows 1-790 of Table 1 at a level that is increased or decreased        relative to the level in a cell not having the neomorphic mutant        SF3B1 protein.

Additional embodiments are set forth in the description which follows.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram depicting modes of alternative splicing.

FIG. 2 is a graph depicting levels of gene expression for abnormallyspliced genes across different cancers in patient samples.

FIG. 3 is a schematic diagram showing the locations of certainneomorphic mutations in the SF3B1 protein and corresponding codingregions of the SF3B1 gene.

FIG. 4 is a graph depicting levels of aberrant splice variants detectedin RNA isolated from pancreatic, lung cancer, and Nalm-6 isogenic celllines using a NanoString® assay. Data are represented as the mean ofthree replicates.

FIG. 5 is a set of western blot images that confirm overexpression ofSF3B1 proteins in 293FT cells.

FIG. 6 is a graph depicting levels of aberrant splice variants in RNAisolated from 293FT cells expressing wild type SF3B1 (SF3B1^(WT)) ormutant SF3B1 proteins, as measured in a NanoString® assay. Data arerepresented as the mean of three replicates.

FIG. 7 is a set of western blot images that confirm overexpression ofSF3B1 proteins in 293FT cells.

FIG. 8 is a graph depicting levels of aberrant splice variants in RNAisolated from 293FT cells expressing SF3B1^(WT) or mutant SF3B1proteins, as measured in a NanoString® assay.

FIG. 9A depicts a set of western blot images showing expression of SF3B1alleles before and after shRNA-knockdown in Panc 05.04 cells. FIG. 9Bdepicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc05.04 cells before and after shRNA-knockdown of all SF3B1 alleles(“SF3B1^(PAN)) or SF3B1^(WT) or mutant SF3B1 (SF3B1^(MUT)) alleles. qPCRdata are represented as fold change relative to pLKO non-treated withdoxycycline (mean±SD, n=3). Solid black, outlined, and gray barsindicate SF3B1^(PAN), SF3B1^(WT), and SF3B1^(MUT) allele-specific qPCRdata, respectively.

FIG. 10A depicts a set of western blot images showing expression ofSF3B1 alleles before and after shRNA-knockdown in Panc 10.05 cells. FIG.10B depicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc10.05 cells before and after shRNA-knockdown of SF3B1 alleles. qPCR dataare represented as fold change relative to pLKO non-treated withdoxycycline (mean±SD, n=3). Solid black, outlined, and gray barsindicate SF3B1^(PAN), SF3B1^(WT), and SF3B1^(MUT) allele-specific qPCRdata, respectively.

FIGS. 11A and 11B are a set of graphs depicting levels of splicevariants in Panc 05.04 (FIG. 11A) and Panc 10.05 cells (FIG. 11B) beforeand after shRNA-knockdown of SF3B1 alleles, as measured in a NanoString®assay. Data are represented as mean of three biological replicates.

FIG. 12 is a set of graphs depicting growth curves of Panc 05.04 cellsbefore (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.

FIG. 13 is a set of graphs depicting growth curves of Panc 10.05 cellsbefore (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.

FIGS. 14A and 14B are a set of images of culture plates showing colonyformation of Panc 05.04 cells (FIG. 14A) and Panc 10.05 (FIG. 14B) cellsbefore and after shRNA-knockdown of SF3B1 alleles.

FIGS. 15A and 15B are a set of graphs showing the level of splicing ofpre-mRNA Ad2 substrate in nuclear extracts from (FIG. 15A) 293F cellsexpressing Flag-tag SF3B1^(WT) or SF3B1^(K700E) (left and right panels[circles and triangles], respectively) and (FIG. 15B) Nalm-6(SF3B1^(WT)) and Nalm-6 SF3B1^(700E) cells (left and right panels[circles and triangles], respectively) treated with varyingconcentrations of E7101. Data are represented as mean±SD, n=2.

FIG. 16A depicts a pair of graphs showing the binding of a radiolabeledE7107 analog to either SF3B1^(WT) (circles, left panel) or SF3B1^(K700E)(triangles, right panel) after incubation of the proteins with varyingconcentrations of E7107. FIG. 16B depicts upper panels, a pair of graphsshowing the levels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA(inverted triangles) in Nalm-6 SF3B1^(K700K) cells (left panel) andNalm-6 SF3B1^(K700E) cells (right panel) treated with varyingconcentrations of E7107, as measured by qPCR. FIG. 16B depicts lowerpanels, a pair of graphs showing the levels of abnormally splicedisoforms of abnormally spliced genes COASY (triangles) and ZDHHC16(diamonds) in Nalm-6 SF3B1^(K700K) cells (left panel) and Nalm-6SF3B1^(K700E) cells (right panel) treated with varying concentrations ofE7107, as measured by qPCR. qPCR data in (FIG. 16B) are represented asmean±SD (n=3).

FIG. 17 is a set of graphs depicting levels of splice variants in Nalm-6SF3B1^(K700K) and Nalm-6 SF3B1^(K700E) cells after treatment of cellswith E7107 for two or six hours, as measured in a NanoString® assay.Data are expressed as fold change from DMSO-only treatment

FIG. 18 is a set of graphs depicting levels of splice variants in Nalm-6SF3B1^(K700K) and Nalm-6 SF3B1^(K700E) cells after treatment of cellswith E7107 for six hours, as measured by RNA-Seq analysis.

FIG. 19 is a set of graphs depicting levels of splice variants in Nalm-6SF3B1^(K700K) and Nalm-6 SF3B1^(K700E) cells after treatment of cellswith the numbered compounds indicated above the graphs, as measured byRNA-Seq analysis.

FIG. 20 is set of graphs depicting levels of splice variants in Nalm-6SF3B1^(K700K) and Nalm-6 SF3B1^(K700E) cells at varying times followingtreatment of cells with E7107, as measured by qPCR of RNA. Data arerepresented as mean±SD (n=3). The upper panels of FIG. 20 depict thelevels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA (invertedtriangles) in Nalm-6 SF3B1^(K700K) cells (left panel) and Nalm-6SF3B1^(K700E) cells (right panel) detected at certain times aftertreatment with E7107. The lower panels of FIG. 20 depict the levels ofabnormally spliced isoforms of abnormally spliced genes COASY(triangles) and ZDHHC16 (diamonds) in Nalm-6 SF3B1^(K700K) cells (leftpanel) and Nalm-6 SF3B1^(K700E) cells (right panel) detected at certaintimes after treatment with E7107. Open circles show the concentration ofE7107 (in μg/ml [right vertical axis]) as determined by massspectrometry of tumor samples.

FIG. 21 is a set of graphs depicting levels of canonical and aberrantsplice variants in Nalm-6 SF3B1^(K700K)- and Nalm-6SF3B1^(K700E)-xenograft tumors (left and right sets of panels,respectively) at certain timepoints after treatment of xenograft micewith E7107, as measured in a NanoString® assay. Data are represented asmean of three replicates.

FIG. 22 is a set of graphs depicting levels of canonical and aberrantsplice variants in Panc 05.04-xenograft tumors at certain timepointsafter treatment of xenograft mice with E7107 at various concentrations,as measured in a NanoString® assay (n=4 mice for each group).

FIG. 23 is a graph depicting tumor volume (shown as mean±SEM) in Nalm-6SF3B1^(K700E)-xenograft mice following treatment with E7107, withcontrol mice treated with vehicle shown by open circles (n=10 animalsfor each group). For E7107-treated animals, inverted triangles=1.25mg/kg, triangles=2.5 mg/kg, and squares=5 mg/kg.

FIG. 24 is a graph depicting survival rates in 10-animal cohorts ofNalm-6 SF3B1^(K700E)-xenograft mice following treatment with E7107, withan untreated cohort shown by the solid black line. For E7107-treatedanimals, dashed line=1.25 mg/kg, gray line=2.5 mg/kg, and dotted line=5mg/kg.

FIG. 25 is set of graphs depicting levels of splice variants inSF3B1^(WT) and neomorphic SF3B1 mutant CLL cell samples followingtreatment with 10 nM E7107 for 6 hours, as measured by analysis. Dataare represented as mean values (n=3).

DESCRIPTION OF THE EMBODIMENTS

In certain aspects, the methods of the invention provide assays formeasuring the amount of a splice variant in a cell, thereby determiningwhether a patient has a cancer with a neomorphic SF3B1 mutation. In someembodiments, at least one of the measured splice variants is an aberrantsplice variant associated with a neomorphic mutation in an SF3B1protein. In additional aspects, the measurement of a splice variant in acell may be used to evaluate the ability of a compound to modulate amutant neomorphic SF3B1 protein in a cell.

To assist in understanding the present invention, certain terms arefirst defined. Additional definitions are provided throughout theapplication.

As used herein, the term “mutant SF3B1 protein” includes SF3B1 proteinsthat differ in amino acid sequence from the human wild type SF3B1protein set forth in SEQ ID NO:1200 (GenBank Accession Number NP_036565,Version NP_036565.2) (S. Bonnal, L. Vigevani, and J. Valcarcel, “Thespliceosome as a target of novel antitumour drugs,” Nat. Rev. DrugDiscov. 11:847-59 [2012]). Certain mutant SF3B1 proteins are“neomorphic” mutants, which refers to mutant SF3B1 proteins that areassociated with differential expression of aberrant splice variants. Incertain embodiments, neomorphic SF3B1 mutants include K700E, K666N,R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C,T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In otherembodiments, neomophic SF3B1 mutants include E622D, E622K, E622Q, E622V,Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D,N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I,T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A,V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V,K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. Certain SF3B1mutations are not associated with expression of aberrant splicevariants, including K700R.

The term “splice variant” as used herein includes nucleic acid sequencesthat span a junction either between two exon sequences or across anintron-exon boundary in a gene, where the junction can be alternativelyspliced. Alternative splicing includes alternate 3′ splice siteselection (“3′ss”), alternate 5′ splice site selection (“5′ss”),differential exon inclusion, exon skipping, and intron retention (FIG.1). Certain splice variants associated with a given genomic location maybe referred to as wild type, or “canonical,” variants. These splicevariants are most abundantly expressed in cells that do not contain aneomorphic SF3B1 mutant protein. Additional splice variants may bereferred to as “aberrant” splice variants, which differ from thecanonical splice variant and are primarily associated with the presenceof a neomorphic SF3B1 mutant protein in a cell. Aberrant splice variantsmay alternatively be referred to as “abnormal” or “noncanonical” splicevariants. In certain circumstances, cells with a wild type ornon-neomorphic SF3B1 protein have low or undetected amounts of anaberrant splice variant, while cells with a neomorphic SF3B1 proteinhave levels of an aberrant splice variant that are elevated relative tothe low or undetected levels in the wild type SF3B1 cells. In somecases, an aberrant splice variant is a splice variant that is present ina wild type SF3B1 cell but is differentially expressed in a cell thathas a neomorphic SF3B1 mutant, whereby the latter cell has a level ofthe aberrant splice variant that is elevated or reduced relative to thelevel in the wild type SF3B1 cell. Different types of cells containing aneomorphic SF3B1 mutant, such as different types of cancer cells, mayhave differing levels of expression of certain aberrant splice variants.In addition, certain aberrant splice variants present in one type ofcell containing a neomorphic SF3B1 mutant may not be present in othertypes of cells containing a neomorphic SF3B1 mutant. In some cases,patients with a neomorphic SF3B1 mutant protein may not express anaberrant splice variant or may express an aberrant splice variant atlower levels, due to low allelic frequency of the neomorphic SF3B1allele. The identity and relative expression levels of aberrant splicevariants associated with various types of cells containing neomorphicSF3B1 mutants, such as certain cancer cells, will be apparent from thedescription and examples provided herein.

The term “evaluating” includes determining the ability of a compound totreat a disease associated with a neomorphic SF3B1 mutation. In someinstances, “evaluating” includes determining whether or to what degree acompound modulates aberrant splicing events associated with a neomorphicSF3B1 protein. Modulation of the activity of an SF3B1 protein mayencompass up-regulation or down-regulation of aberrant splice variantexpression associated with a neomorphic SF3B1 protein. Additionally,“evaluating” includes distinguishing patients that may be successfullytreated with a compound that modulates the expression of splice variantsassociated with a neomorphic SF3B1 protein.

The use of the word “a”, “an” or “the” when used in conjunction with theterm “comprising” in the claims or the specification may mean “one,” butit is also consistent with the meaning of “one or more,” “at least one,”and “one or more than one.” “Or” is to be read inclusively to mean“and/or” unless explicitly indicated to refer to alternatives only, suchas where alternatives are mutually exclusive.

Splice Variants

Splice variants of the invention are listed in Table 1. Table 1 providesthe genomic location of each canonical (“WT”) and aberrant (“Ab.”)splice junction, as well as the sequence. Each sequence listed in thetable contains 20 nucleotides from each of the 3′ and 5′ sides of asplice junction (i.e., the splice junction is at the midpoint of thelisted nucleotide sequence). The “Avg WT %” and “Avg Ab. %” columnsprovide the average percentage count that the canonical (WT) or aberrantsplice variant, respectively, represented out of the total counts of allsplice variants that utilize a shared splice site, where the counts weredetermined as set forth in Example 1. The “Loge Fold Change” columnprovides the loge of the fold change observed between percentage countsof canonical and aberrant cohorts (see Example 1). The “FDR Q-Value”column provides, as a measure of statistical significance, q-valuescalculated using the Benjamini-Hochberg procedure from p-values, whichin turn were determined using the moderated t-test defined in theBioconductor's limma package (see Example 1). The “Event” columnindicates the nature of the aberrant splice variant, where “3′ss”indicates alternate 3′ splice site selection, “5′ss” indicates alternate5′ splice site selection, “exon incl.” indicates differential exoninclusion, and “exon skip” indicates exon skipping. The “Type” columnrefers to the cancer type of the sample in which the aberrant splicevariant was identified, where “Br.” indicates breast cancer, “CLL”indicates chronic lymphocytic leukemia, and “Mel.” indicates melanoma.

TABLE 1 Aberrant Avg Avg Log2 Aberrant sequence (SEQ WT sequence WT Ab.Fold FDR Q- junction WT junction ID NO) (SEQ ID NO) % % Diff. ValueEvent Type 1 chr2: chr2: AGCAAGTAGAAG AGCAAGTAGAAG 0 56 5.83 6.30E−073′ss Br. 109102364-109102954 109102364-109102966 TCTATAAAATTTTCTATAAAATAC ACCCCCAGATAC AGCTGGCTGAAA AGCT (1) TAAC (2) 2 chr16: chr16:CGGGCCGCATCA CGGGCCGCATCA 0 51 5.70 2.38E−07 3′ss Br. 708344-708509708344-708524 TCCGGGAGAGCA TCCGGGAGCTGC CTGTGTTCCAGC CCGGTGTCCACC TGCC(3) CTGA (4) 3 chr3: chr3: CTGGAGCCGGCG CTGGAGCCGGCG 0 51 5.70 2.19E−073′ss Br. 50380021-50380348 50380000-50380348 GGAAGGAGTGTG GGAAGGAGGCAACTGGTTCCTCTC GCTGCAGCAGTT CCCA (5) CGAG (6) 4 chr19: chr19: GGCCCTTTTGTCGGCCCTTTTGTC 0 48 5.61 2.32E−06 3′ss Br. 57908542-5790978057908542-57909797 CTCACTAGCATT CTCACTAGGTTC TCTGTTCTGACA TTGGCATGGAGCGGTT (7) TGAG (8) 5 chr2: chr2: TGGGAGGAGCAT TGGGAGGAGCAT 0 47 5.587.79E−07 3′ss Br. 97285513-97297048 97285499-97297048 GTCAACAGAGTTGTCAACAGGACT TCCCTTATAGGA GGCTGGACAATG CTGG (9) GCCC (10) 6 chr19:chr19: GATGGTGGATGA GATGGTGGATGA 0 46 5.55 1.10E−05 3′ss Br.23545541-23556543 23545527-23556543 ACCCACAGTTTT ACCCACAGGTATTTTTTTTCAGGT ATGTCCTCATTT ATAT (11) TCCT (12) 7 chr10: chr10:TACCTCTGGTTC TACCTCTGGTTC 0 46 5.55 3.63E−09 3′ss Br. 99214556-9921539599214556-99215416 CTGTGCAGTCTT CTGTGCAGTTCT CGCCCCTCTTTT GTGGCACTTGCCCTTA (13) CTGG (14) 8 chr18: chr18: TTGGACCGGAAA TTGGACCGGAAA 0 44 5.494.30E−09 3′ss Br. 683395-685920 683380-685920 AGACTTTGAGTC AGACTTTGATGATCTTTTTGCAGA TGGATGCCAACC TGAT (15) AGCG (16) 9 chr17: chr17:ACCCAAGCCTTG ACCCAAGCCTTG 0 44 5.49 1.50E−07 exon Br. 40714237-4071437340714237-40714629 AGGTTTCATTTC AGGTTTCAGCCT incl. CCCCTCCCAGGAGGGCAGCATGGC TTTC (17) CGTA (18) 10 chr5: chr5: AGCATTGCTAGAAGCATTGCTAGA 0 41 5.39 4.86E−09 3′ss Br. 139815842-139818078139815842-139818045 AGCAGCAGCTTT AGCAGCAGGAAT TGCAGATCCTGA TGGCAAATTGTCGGTA (19) AACT (20) 11 chr1: chr1: CAAGTATATGAC CAAGTATATGAC 0 39 5.321.31E−10 3′ss Br. 245246990-245288006 245246990-245250546 TGAAGAAGATCCTGAAGAAGGTGA TGAATTCCAGCA GCCTTTTTCTCA AAAC (21) AGAG (22) 12 chr3:chr3: TGCAGTTTGGTC TGCAGTTTGGTC 0 36 5.21 9.63E−09 3′ss Br.9960293-9962150 9960293-9962174 AGTCTGTGCCTT AGTCTGTGGGCT CCTCACCCCTCTCTGTGGTATATG CCTC (23) ACTG (24) 13 chr1: chr1: TCTTTGGAAAATTCTTTGGAAAAT 0 29 4.91 3.27E−07 3′ss Br. 101458310-101460665101458296-101460665 CTAATCAATTTT CTAATCAAGGGA CTGCCTATAGGG AGGAAGATCTATGAAG (25) GAAC (26) 14 chr7: chr7: GTATCAAAGTGT GTATCAAAGTGT 0 28 4.865.02E−05 3′ss Br. 94157562-94162500 94157562-94162516 GGACTGAGATTTGGACTGAGGATT GTCTTCCTTTAG CCATTGCAAAGC GATT (27) CACA (28) 15 chr20:chr20: AGAACTGCACCT AGAACTGCACCT 0 27 4.81 1.50E−07 3′ss Br.62701988-62703210 62701988-62703222 ACACACAGCCCT ACACACAGGTGCGTTCACAGGTGC AGACCCGCAGCT AGAC (29) CTGA (30) 16 chr17: chr17:GGAGCAGTGCAG GGAGCAGTGCAG 0 25 4.70 9.63E−06 3′ss Br. 71198039-7119916271198039-71199138 TTGTGAAATCAT TTGTGAAAGTTT TACTTCTAGATG TGATTCATGGATATGC (31) TCAC (32) 17 chr17: chr17: CTATTTCACTCT CTATTTCACTCT 0 25 4.705.99E−08 3′ss Br. 7131030-7131295 7131102-7131295 CCCCCGAACCTACCCCCGAAATGA TCCAGGTTCCTC GCCCATCCAGCC CTCC (33) AATT (34) 18 chr20:chr20: TTTGCAGGGAAT TTTGCAGGGAAT 0 25 4.70 2.72E−07 3′ss Br.35282126-35284762 35282104-35284762 GGGCTACATCCC GGGCTACATACCCTTGGTTCTCTG ATCTGCCAGCAT TTAC (35) GACT (36) 19 chr2: chr2:TGACCACGGAGT TGACCACGGAGT 0 25 4.70 1.61E−06 3′ss Br.232196609-232209660 232196609-232209686 ACCTGGGGCCCT ACCTGGGGATCATTTTTCTCTTTC TGACCAACACGG CTTC (37) GGAA (38) 20 chr17: chr17:AGACCTACCAGA AGACCTACCAGA 0 24 4.64 7.16E−06 3′ss Br. 62574712-6257690662574694-62576906 AGGCTATGTGTT AGGCTATGAACA TATTAATTTTAC GAGGACAACGCAAGAA (39) ACAA (40) 21 chr12: chr12: ATTTGGACTCGC ATTTGGACTCGC 0 23 4.588.14E−08 3′ss Br. 105601825-105601935 105601807-105601935 TAGCAATGATGTTAGCAATGAGCA CTGTTTATTTTT TGACCTCTCAAT AGAG (41) GGCA (42) 22 chr12:chr12: CATGTGGAATCC CATGTGGAATCC 0 22 4.52 1.87E−04 3′ss Br.53836517-53837270 53836517-53837174 CAATGCCGGCCC CAATGCCGGGCACTGTCCTCCTCC GCCAGGGCCAAA CCCA (43) TCCA (44) 23 chr22: chr22:CTGGGAGGTGGC CTGGGAGGTGGC 0 22 4.52 2.76E−08 3′ss Br. 19044699-1905071419044675-19050714 ATTCAAAGCCCC ATTCAAAGGCTC ACCTTTTGTCTC TTCAGAGGTGTTCCCA (45) CCTG (46) 24 chr11: chr11: GGATGACCGGGA GGATGACCGGGA 0 21 4.464.61E−08 3′ss Br. 71939542-71939690 71939542-71939770 TGCCTCAGTCACTGCCTCAGATGG TTTACAGCTGCA GGAGGATGAGAA TCGT (47) GCCC (48) 25 chr20:chr20: ACATGAAGGTGG ACATGAAGGTGG 0 21 4.46 2.63E−08 3′ss Br.34144042-34144725 34144042-34144743 ACGGAGAGGCTC ACGGAGAGGTACCCCTCCCACCCC TGAGGACAAATC AGGT (49) AGTT (50) 26 chr6: chr6:AGAGAAGTCGTT AGAGAAGTCGTT 2 64 4.44 2.91E−10 3′ss Br. 31919381-3191956531919381-31919651 TCATTCAAGTCA TCATTCAAGTTG GCTAAGACACAA GTGTAATCAGCTGCAG (51) GGGG (52) 27 chr1: chr1: TCACTCAAACAG TCACTCAAACAG 0 20 4.399.99E−07 3′ss Br. 179835004-179846373 179834989-179846373 TAAACGAGTTTTTAAACGAGGTAT ATCATTTACAGG GTGACGCATTCC TATG (53) CAGA (54) 28 chr1:chr1: CGATCTCCCAAA CGATCTCCCAAA 0 20 4.39 1.35E−09 3′ss Br.52880319-52880412 52880319-52880433 AGGAGAAGTCTG AGGAGAAGCCCCACCAGTCTTTTC TCCCCTCGCCGA TACA (55) GAAA (56) 29 chr8: chr8:TTATTTTACACA TTATTTTACACA 0 20 4.39 1.49E−09 3′ss Br. 38095145-3809562438095145-38095606 ATCCAAAGCCAG ATCCAAAGCTTA TTGCAGGGTCTG TGGTGCATTACCATGA (57) AGCC (58) 30 chr19: chr19: TGCCTGTGGACA TGCCTGTGGACA 0 19 4.322.37E−05 3′ss Br. 14031735-14034130 14031735-14034145 TCACCAAGCCTCTCACCAAGGTGC GTCCTCCCCAGG CGCCTGCCCCTG TGCC (59) TCAA (60) 31 chr14:chr14: AGTTAGAATCCA AGTTAGAATCCA 0 18 4.25 1.65E−10 3′ss Br.74358911-74360478 74358911-74360499 AACCAGAGTGTT AACCAGAGCTCCGTCTTTTCTCCC TGGTACAGTTTG CCCA (61) TTCA (62) 32 chr19: chr19:ATATGCTGGAAT ATATGCTGGAAT 0 18 4.25 8.07E−08 3′ss Br. 45314603-4531548245314603-45315419 GGTTCCTTGTCA GGTTCCTTACCG CAATGCACGACA ACCGCTCGGGAGCCCG (63) CTCG (64) 33 chr1: chr1: ATCAGAAATTCG ATCAGAAATTCG 0 18 4.254.25E−08 3′ss Br. 212515622-212519131 212515622-212519144 TACAACAGGTTTTACAACAGCTCC CTTTTAAAGCTC TGGAGCTTTTTG CTGG (65) ATAG (66) 34 chr9:chr9: AAATGAAGAAAC AAATGAAGAAAC 0 18 4.25 1.31E−10 3′ss Br.125759640-125760854 125759640-125760875 TCCTAAAGCCTC TCCTAAAGATAATCTCTTTCTTTG AGTCCTGTTTAT TTTA (67) GACC (68) 35 chr11: chr11:CATAAAATTCTA CATAAAATTCTA 0 17 4.17 1.35E−06 3′ss Br. 4104212-41044714104212-4104492 ACAGCTAATTCT ACAGCTAAGCAA CTTTCCTCTGTC GCACTGAGCGAG TTCA(69) GTGA (70) 36 chr12: chr12: GCCTGCCTTTGA GCCTGCCTTTGA 0 17 4.173.58E−07 3′ss Br. 113346629-113348840 113346629-113348855 TGCCCTGGATTTTGCCCTGGGTCA TGCCCGAACAGG GTTGACTGGCGG TCAG (71) CTAT (72) 37 chr17:chr17: CCAAGCTGGTGT CCAAGCTGGTGT 0 17 4.17 4.19E−04 3′ss Br.78188582-78188831 78188564-78188831 GCGCACAGGCCT GCGCACAGGCATCTCTTCCCGCCC CATCGGGAAGAA AGGC (73) GCAC (74) 38 chr20: chr20:CTCCTTTGGGTT CTCCTTTGGGTT 0 17 4.17 2.67E−07 3′ss Br. 45354963-4535545345354963-45355502 TGGGCCAGGCCC TGGGCCAGTGAC CAGGTCCCACCA CTGGCTTGTCCTCAGC (75) CAGC (76) 39 chr12: chr12: AATATTGCTTTA AATATTGCTTTA 0 16 4.092.79E−07 3′ss Br. 116413154-116413319 116413118-116413319 CCAAACAGGGACCCAAACAGGTCA CCCTTCCCCTTC CGGAGGAGTAAA CCCA (77) GTAT (78) 40 chr14:chr14: CAGTTATAAACT CAGTTATAAACT 0 16 4.09 4.46E−07 3′ss Br.71059726-71060012 71059705-71060012 CTAGAGTGAGTT CTAGAGTGCTTATATTTTCCTTTT CTGCAGTGCATG ACAA (79) GTAT (80) 41 chr16: chr16:GCCTGCCCCGGA GCCTGCCCCGGA 0 15 4.00 7.77E−06 3′ss Br. 30012851-3001668830012851-30016541 AACTCAAGATGT AACTCAAGATGG TCAGCGATGCAG CGGTGGGACCCCGTAG (81) CCGA (82) 42 chr17: chr17: TTCAGGAGGTGG TTCAGGAGGTGG 0 15 4.003.26E−05 3′ss Br. 57148329-57153007 57148308-57153007 AGCACCAGATAAAGCACCAGTTGC TTTTTTTCCTCA GGTCTTGTAGTA CACA (83) AGAG (84) 43 chr16:chr16: GGATCCTTCACC GGATCCTTCACC 0 14 3.91 3.01E−07 3′ss Br.1402307-1411686 1402307-1411743 CGTGTCTGTCTT CGTGTCTGGACC TGCAGACAGGTTCGTGCATCTCTT CTGT (85) CCGA (86) 44 chr3: chr3: ATTTGGATCCTGATTTGGATCCTG 0 14 3.91 8.71E−07 3′ss Br. 196792335-196792578196792319-196792578 TGTTCCTCTTTT TGTTCCTCATAC TTTCTGTTAAAG AACTAGACCAAAATAC (87) ACGA (88) 45 chr14: chr14: AGATGTCAGGTG AGATGTCAGGTG 0 13 3.811.55E−05 3′ss Br. 75356052-75356580 75356052-75356599 GGAGAAAGCCTTGGAGAAAGCTGT TGATTGTCTTTT TGGAGACACAGT CAGC (89) TGCA (90) 46 chr18:chr18: AGAAAGAGCATA AGAAAGAGCATA 0 13 3.81 9.84E−07 3′ss Br.33605641-33606862 33573263-33606862 AATTGGAAATAT AATTGGAAGAGTTGGACATGGGCG ACAAGCGCAAGC TATC (91) TAGC (92) 47 chr1: chr1:TCAGCCCTCTGA TCAGCCCTCTGA 0 13 3.81 6.10E−07 3′ss Br.226036315-226036597 226036255-226036597 ACTACAAAGGTG ACTACAAAACAGTTTGTTCACAGA AAGAGCCTGCAA GATC (93) GTGA (94) 48 chr6: chr6:CCGGGGCCTTCG CCGGGGCCTTCG 3 51 3.70 1.35E−09 3′ss Br. 10723474-1072478810723474-10724802 TGAGACCGCTTG TGAGACCGGTGC TTTTCTGCAGGT AGGCCTGGGGTAGCAG (95) GTCT (96) 49 chr2: chr2: CAAGTCCATCTC CAAGTCCATCTC 0 12 3.705.71E−03 3′ss Br. 132288400-132289210 132288400-132289236 TAATTCAGGGTCTAATTCAGGCAA TGACTTGCAGCC GGCCAGGCCCCA AACT (97) GCCC (98) 50 chr2:chr2: CAAGATAGATAT CAAGATAGATAT 0 12 3.70 4.26E−06 3′ss Br.170669034-170671986 170669016-170671986 TATAGCAGGTGG TATAGCAGAACTCTTTTGTTTTAC TCGATATGACCT AGAA (99) GCCA (100) 51 chr15: chr15:GAAACCAACTAA GAAACCAACTAA 1 24 3.64 4.30E−09 3′ss Br. 59209219-5922455459209198-59224554 AGGCAAAGCCCA AGGCAAAGGTAA TTTTCCTTCTTT AAAACATGAAGCCGCA (101) AGAT (102) 52 chr11: chr11: GGGGACAGTGAA GGGGACAGTGAA 0 113.58 5.99E−08 3′ss Br. 57100545-57100908 57100623-57100908 ATTTGGTGGCAAATTTGGTGGGCA GAATGAGGTGAC GCTGCTTTCCTT ACTG (103) TGAC (104) 53 chr1:chr1: CTCAGAGCCAGG CTCAGAGCCAGG 0 11 3.58 3.15E−07 3′ss Br.35871069-35873587 35871069-35873608 CTGTAGAGATGT CTGTAGAGTCCGTTTCTACCTTTC CTCTATCAAGCT CACA (105) GAAG (106) 54 chr2: chr2:GAGGAGCCACAC GAGGAGCCACAC 0 11 3.58 2.22E−07 3′ss Br.220044485-220044888 220044485-220044831 TCTGACAGATAC TCTGACAGTGAGCTGGCTGAGAGC GGTGCGGGGTCA TGGC (107) GGCG (108) 55 chr5: chr5:ACTCGCGCCTCT ACTCGCGCCTCT 0 11 3.58 7.04E−07 3′ss Br.150411955-150413168 150411944-150413168 TCCATCTGTTTT TCCATCTGCCGGGTCGCAGCCGGA AATACACCTGGC ATAC (109) GTCT (110) 56 chrX: chrX:ACTTCCTTAGTG ACTTCCTTAGTG 0 11 3.58 7.37E−07 3′ss Br. 47059013-4705980847059013-47060292 GTTTCCAGGTTG GTTTCCAGGTGG CCAGGGCACTGC TGGTGCTCACCAAGCT (111) ACAC (112) 57 chrX: chrX: GTCTTGAGAATT ACTTCCTTAGTG 0 11 3.586.70E−06 5′ss Br. 47059943-47060292 47059013-47060292 GGAAGCAGGTGGGTTTCCAGGTGG TGGTGCTCACCA TGGTGCTCACCA ACAC (113) ACAC (112) 58 chr20:chr20: TCCAGAGCCCAC TCCAGAGCCCAC 2 34 3.54 4.87E−09 3′ss Br.330007-330259 330007-330281 AGTCCCAGCTGC AGTCCCAGGGGT ACCTTACCTGCTCCATGATGCCGA CCCC (114) GCTG (115) 59 chr18: chr18: CCAAGTTTTGTGCCAAGTTTTGTG 1 22 3.52 1.96E−05 3′ss Br. 224200-224923 224179-224923AAAGAAAGTGTA AAAGAAAGAACA TGTTTTGTTCAC TCAGATACCAAA GACA (116) CCTA(117) 60 chr11: chr11: TCTTCACAGAAC TCTTCACAGAAC 0 10 3.46 2.99E−08 3′ssBr. 47195466-47196565 47195391-47196565 ACACTCAAGTGC ACACTCAACCCCTTGTAGGTCTTG CTGCCTGGGATG GTGC (118) CGCC (119) 61 chr12: chr12:GAGAAGCTCACG TCTTGGAGGAGC 0 10 3.46 4.11E−02 exon Br. 56604352-5660677956604352-56607741 ATTACCAGGCAC CAGTACAGGCAC incl. CTCATTGTGAACCTCATTGTGAAC ATGC (120) ATGC (121) 62 chr14: chr14: GTGGGGGGCCATGTGGGGGGCCAT 0 10 3.46 3.25E−08 3′ss Br. 23237380-2323898523237380-23238999 TGCTGCATTTTG TGCTGCATGTAC TATTTTCCAGGT AGTCTTTGCCCGACAG (122) CTGC (123) 63 chr17: chr17: TACTGAAATGTG TACTGAAATGTG 0 103.46 2.49E−05 3′ss Br. 34942628-34943454 34942628-34943426 ATGAACATATCCATGAACATATCC AGGTAATCGAGA AGAAGCTTGGAA GACC (124) GCTG (125) 64 chr1:chr1: GAATCTCTTATC GAATCTCTTATC 0 10 3.46 2.93E−06 3′ss Br.145581564-145583935 145581564-145583914 ATTGATGGTTCC ATTGATGGTTTATGTTCAGATTGT TTTATGGAGATT GATG (126) CTTA (127) 65 chr5: chr5:CTCCATGCTCAG CTCCATGCTCAG 1 20 3.39 6.76E−06 3′ss Br. 869519-870587865696-870587 CTCTCTGGTTTC CTCTCTGGGGAA TTTCAGGGCCTG GGTGAAGAAGGA CCAT(128) GCTG (129) 66 chr12: chr12: CTTGGAGCTGAC CTTGGAGCTGAC 7 79 3.321.30E−08 3′ss Br. 107378993-107380746 107379003-107380746 GCCGACGGGGAAGCCGACGGTTTA CTGACAAGATCA TTGCAGGGAACT CATT (130) GACA (131) 67 chr7:chr7: TCCAGCCTGGGC CTATCAAAAGAG 1 19 3.32 4.35E−08 exon Br.8261028-8267267 8261028-8268230 GACAGAAGTCTT GATATGTTTCTT incl.GTCTCAAGAAGA GTCTCAAGAAGA AAAC (132) AAAC (133) 68 chr10: chr10:TGCGGAGCAAGA TGCGGAGCAAGA 0 9 3.32 1.37E−04 3′ss Br. 5497081-54980275497081-5498049 GTGGACATCGTT GTGGACATAAAC TGTTTCCCATTT TTTACATTTTCC CTCC(134) TGTT (135) 69 chr11: chr11: AGTCCAGCCCCA AGTCCAGCCCCA 0 9 3.324.66E−07 3′ss Br. 64900740-64900940 64900723-64900940 GCATGGCACCTCGCATGGCAGTCC TCCCCACTCCTA TGTACATCCAGG GGTC (136) CCTT (137) 70 chr19:chr19: CAAGCAGGTCCA CAAGCAGGTCCA 0 9 3.32 1.49E−09 3′ss Br.5595521-5598803 5595508-5598803 AAGAGAGATTTT AAGAGAGAAGCT GGTAAACAGAGCCCAAGAGTCAGG TCCA (138) ATCG (139) 71 chr22: chr22: CTCTCTCCAACCCTCTCTCCAACC 0 9 3.32 8.58E−06 3′ss Br. 39064137-3906687439064137-39066888 TGCATTCTCATC TGCATTCTTTGG TCGCCCACAGTT ATCGATCAACCCGGAT (140) GGGA (141) 72 chr9: chr9: CACCACGCCGAG CACCACGCCGAG 2 28 3.272.13E−08 3′ss Br. 125023777-125026993 125023787-125026993 GCCACGAGACATGCCACGAGTATT TGATGGAAGCAG TCATAGACATTG AAAC (142) ATGG (143) 73 chr15:chr15: GCCTCACTGAGC GCCTCACTGAGC 1 18 3.25 5.94E−09 exon Br.25207356-25212175 25207356-25213078 AACCAAGAGTAG AACCAAGAGTGT incl.TGACTTGTCAGG CAGTTGTACCCG AGGA (144) AGGC (145) 74 chr9: chr9:GGGAGATGGATA GGGAGATGGATA 3 35 3.17 6.19E−08 3′ss Br. 35813153-3581326235813142-35813262 CCGACTTGCTCA CCGACTTGTGAT ATTTCAGTGATC CAACGATGGGAAAACG (146) GCTG (147) 75 chr6: chr6: AGGATGTGGCTG AGGATGTGGCTG 1 17 3.175.18E−06 3′ss Br. 31602334-31602574 31602334-31602529 GCACAGAAGTGTGCACAGAAATGA CATCAGGTCCCT GTCAGTCTGACA GCAG (148) GTGG (149) 76 chr11:chr11: TTCTCCAGGACC TTCTCCAGGACC 0 8 3.17 6.00E−04 3′ss Br.125442465-125445146 125442465-125445158 TTGCCAGACCTT TTGCCAGAGGAATTCTATAGGGAA TCAAAGACTCCA TCAA (150) TCTG (151) 77 chr13: chr13:AGCTGAAATTTC AGCTGAAATTTC 0 8 3.17 1.20E−06 3′ss Br. 113915073-113917776113915073-113917800 CAGTAAAGGGGG CAGTAAAGCCTG GTTTTATTCTTC GAGATTTGAAAATTTT (152) AGAG (153) 78 chr16: chr16: GATGTCACTGTG GATGTCACTGTG 0 83.17 4.76E−02 3′ss Br. 14966186-14968874 14966186-14968892 ACTATCAAGGGCACTATCAAGTCT CGTCTTTCTTCT TCCATCGACAGT AGGT (154) GAAC (155) 79 chr2:chr2: TATCCATTCCTG TATCCATTCCTG 0 8 3.17 2.22E−07 3′ss Br.178096758-178097119 178096736-178097119 AGTTACAGTATA AGTTACAGTGTCAACTTCCTTCTC TTAATATTGAAA ATGC (156) ATGA (157) 80 chrX: chrX:TACAAGAGCTGG TACAAGAGCTGG 0 8 3.17 2.14E−05 3′ss Br. 153699660-153699819153699660-153699830 GTGGAGAGGGTC GTGGAGAGGTAT CCAACAGGTATT TATCGAGACATTATCG (158) GCAA (159) 81 chr19: chr19: AGCCATTTATTT AGCCATTTATTT 3 313.00 7.42E−06 3′ss Br. 9728842-9730107 9728855-9730107 GTCCCGTGGGAAGTCCCGTGGGTT CCAATCTGCCCT TTTTTCCAGGGA TTTG (160) ACCA (161) 82 chr1:chr1: AGTTACAACGAA AGTTACAACGAA 2 23 3.00 8.51E−06 3′ss Br.185056772-185060696 185056772-185060710 CACCTCAGTGAC CACCTCAGGAGGTCTTTTACAGGA CAATAACAGATG GGCA (162) GCTT (163) 83 chr15: chr15:TCACACAGGATA GCCTCACTGAGC 1 15 3.00 3.25E−08 exon Br. 25212299-2521307825207356-25213078 ATTTGAAAGTGT AACCAAGAGTGT incl. CAGTTGTACCCGCAGTTGTACCCG AGGC (164) AGGC (145) 84 chr11: chr11: CGGCGCGGGCAACGGCGCGGGCAA 0 7 3.00 1.28E−08 3′ss Br. 62648919-6264935262648919-62649364 CCTGGCGGCCCC CCTGGCGGGTCT CATTTCAGGTCT GAAGGGGCGTCTGAAG (165) CGAT (166) 85 chr11: chr11: CCACCGCCATCG CCACCGCCATCG 0 73.00 4.87E−09 3′ss Br. 64877395-64877934 64877395-64877953 ACGTGCAGTACCACGTGCAGGTGG TCTTTTTACCAC GGCTCCTGTACG CAGG (167) AAGA (168) 86 chr19:chr19: CTATGGGCTCAC CTATGGGCTCAC 0 7 3.00 1.24E−03 3′ss Br.41084118-41084353 41084118-41084367 TCCTCTGGTCCT TCCTCTGGTTCGCCTGTTGCAGTT TCGCCTGCAGCT CGTC (169) TCGA (170) 87 chr1: chr1:TATCTCTGGGAA TATCTCTGGGAA 0 7 3.00 3.66E−06 3′ss Br. 35917392-3591915735917377-35919157 AAAACACATTTC AAAACACAGGGA TTTTTTTGCAGG CCTGATGGGGTGGGAC (171) CAGC (172) 88 chr22: chr22: TCATCCAGAGCC TCATCCAGAGCC 0 73.00 1.95E−06 3′ss Br. 50966161-50966940 50966146-50966940 CAGAGCAGGGGACAGAGCAGATGC TGTCTGACCAGA AAGTGCTGCTGG TGCA (173) ACCA (174) 89 chr9:chr9: CCAAGGACTGCA CCAAGGACTGCA 0 7 3.00 8.14E−08 3′ss Br.139837449-139837800 139837395-139837800 CTGTGAAGGCCC CTGTGAAGATCTCCGCCCCGCGAC GGAGCAACGACC CTGG (175) TGAC (176) 90 chr1: chr1:CCCGAGCTCAGA CCCGAGCTCAGA 4 38 2.96 2.79E−08 3′ss Br. 3548881-35499613548902-3549961 GAGTAAATTCTC GAGTAAATATGA CTTACAGACACT GATCGCCTCTGT GAAA(177) CCCA (178) 91 chr19: chr19: GTGCTTGGAGCC GTGCTTGGAGCC 3 29 2.913.56E−07 3′ss Br. 55776746-55777253 55776757-55777253 CTGTGCAGACTTCTGTGCAGCCTG TCCGCAGGGTGT GTGACAGACTTT GCGC (179) CCGC (180) 92 chr1:chr1: GCTGGACACGCT GCTGGACACGCT 1 14 2.91 2.38E−07 exon Br.39332671-39338689 39333282-39338689 GACCAAGGCATC GACCAAGGTGTT skipACTTAGGAGCTG GGTAGCCTTATA CTAC (181) TGAA (182) 93 chr2: chr2:CCCCTGAGATGA CCCCTGAGATGA 1 14 2.91 1.82E−07 exon Br. 27260570-2726068227260570-27261013 AGAAAGAGCTCC AGAAAGAGCTCC incl. CTGTTGACAGCTTGAGCAGCCTGA GCCT (183) CTGA (184) 94 chr2: chr2: CTGAACTTTGGGCTGAACTTTGGG 3 28 2.86 7.09E−06 3′ss Br. 233599948-233600472233599948-233612324 CCTGAATGATGT CCTGAATGGCTC GTTTGGACCCCG CGAGCTCTGTCCAATA (185) AGTG (186) 95 chr11: chr11: AGATCGCCTGGC AGATCGCCTGGC 0 62.81 4.87E−09 3′ss Br. 3697619-3697738 3697606-3697738 TCAGTCAGTTTTTCAGTCAGACAT TCTCTCTAGACA GGCCAAACGTGT TGGC (187) AGCC (188) 96 chr11:chr11: GGAGGTGGACCT GGAGGTGGACCT 0 6 2.81 1.25E−06 3′ss Br.68363686-68367788 68363686-68367808 GAGTGAACAATT GAGTGAACCACCTCTCCCCTCTTT CAACTGGTCAGC TTAG (189) TAAC (190) 97 chr12: chr12:TACAGATGGTAA TACAGATGGTAA 0 6 2.81 8.19E−07 3′ss Br. 72315234-7231674372315234-72316762 AATGCAAGTTTG AATGCAAGGAAT ATTTTTCATATC TGCCACAAGCAGCAGG (191) TCTG (192) 98 chr16: chr16: CCCTGCTCATCA CCCTGCTCATCA 0 62.81 5.11E−07 3′ss Br. 685022-685280 684956-685280 CCTACGGGTCTGCCTACGGGCCCT TCCCAGGCTCTC ATGCCATCAATG TGGG (193) GGAA (194) 99 chr1:chr1: GGCTCCCATTCT GGCTCCCATTCT 0 6 2.81 3.43E−04 3′ss Br.155630724-155631097 155630704-155631097 GGTTAAAGAGTG GGTTAAAGGCCATTCTCATTTCCA GTCTGCCATCCA ATAG (195) TCCA (196) 100 chr1: chr1:CTGCACTTATAA CTGCACTTATAA 0 6 2.81 1.50E−06 3′ss Br. 47108988-4711083247108973-47110832 ATATTCAGTGTT ATATTCAGACCC CCACCTTGCAGA GAGGGGAAGCTGCCCG (197) CAGC (198) 101 chr22: chr22: CGCTGGCACCAT CGCTGGCACCAT 0 62.81 1.29E−02 3′ss Br. 36627480-36629198 36627512-36629198 GAACCCAGTATTGAACCCAGAGAG TCCAGGACCAAG CAGTATCTTTAT TGAG (199) TGAG (200) 102 chr6:chr6: CCCTAGTCTGAT AGAGAAGTCGTT 0 6 2.81 6.01E−04 5′ss Br.31919565-31919651 31919381-31919651 TCCTTTAGGTTG TCATTCAAGTTGGTGTAATCAGCT GTGTAATCAGCT GGGG (201) GGGG (52) 103 chr1: chr1:TTCCCCATCAAC TTCCCCATCAAC 3 26 2.75 6.26E−07 3′ss Br. 19480448-1948141119480433-19481411 ATCAAAAGTTTT ATCAAAAGTTCC GTTGTCTGCAGT AATGGTGGCAGTTCCA (202) AAGA (203) 104 chr11: chr11: CCAGCTGCATTG CCAGCTGCATTG 4 322.72 6.93E−04 3′ss Br. 67161081-67161193 67161081-67161161 CAAGTTCGGACTCAAGTTCGGGGT GTGAGTCCCTGC GCGGAAGACTCA AGGC (204) CAAC (205) 105 chr12:chr12: GGCCAGCCCCCT GGCCAGCCCCCT 6 41 2.58 1.26E−09 3′ss Br.120934019-120934204 120934019-120934218 TCTCCACGGCCT TCTCCACGGTAATGCCCACTAGGT CCATGTGCGACC AACC (206) GAAA (207) 106 chr14: chr14:CGCTCTCCGCCT AGGGAGACGTTC 2 17 2.58 1.96E−05 exon Br. 75348719-7535228875349327-75352288 TCCAGAAGGGGT CCTGCCTGGGGT skip CTCCTTATGCCACTCCTTATGCCA GGGA (208) GGGA (209) 107 chr1: chr1: TTGGAAGCGAATTTGGAAGCGAAT 1 11 2.58 1.14E−07 3′ss Br. 23398690-2339976623398690-23399784 CCCCCAAGTCCT CCCCCAAGTGAT TTGTTCTTTTGC GTATATCTCTCAAGTG (210) TCAA (211) 108 chr11: chr11: CTACGGCGGTGC CTACGGCGGTGC 0 52.58 1.09E−07 3′ss Br. 44957237-44958353 44957213-44958353 CCTCCTCACCCCCCTCCTCAGCAT CTTTTCATCCCC CTCCCTGATCAT CGCC (212) GTGG (213) 109 chr12:chr12: CCTGGTCGCAGT CCTGGTCGCAGT 0 5 2.58 9.89E−04 exon Br.57494682-57496072 57493873-57496072 TCAACAAGATGA TCAACAAGGAGA incl.GGAATCTGATGC TCCTGCTGGGCC TCAG (214) GTGG (215) 110 chr16: chr16:CACCAAGCAGAG CACCAAGCAGAG 0 5 2.58 1.04E−07 3′ss Br. 15129410-1512985215129410-15129872 GCTTCCAGTCTG GCTTCCAGGCCA TCTGCCCTTTCT GAAGCCTTTTAAGTAG (216) AAGG (217) 111 chr17: chr17: GGGACTCCCCCA GGGACTCCCCCA 0 52.58 9.75E−05 3′ss Br. 41164294-41164946 41164294-41165063 AAGACAAGCTTTAAGACAAGGTCC TCTTTCAGTAAA CATTTTCAGTGC TGTA (218) CCAA (219) 112 chr17:chr17: GCACTGCTGTTC GCACTGCTGTTC 0 5 2.58 1.25E−05 3′ss Br.61511981-61512446 61511955-61512446 AACCTCGGCTTC AACCTCGGGGGCTCCCTTCCTCTC AAGTATAGCGCA ACCC (220) TTTG (221) 113 chr19: chr19:ACGAGACCATTG ACGAGACCATTG 0 5 2.58 1.71E−05 3′ss Br. 2247021-22475642247021-2247592 CCTTCAAGGAGC CCTTCAAGGTGC CCTCTCTGTCCC CGAGCAGAGAGA CCGC(222) TCGA (223) 114 chr21: chr21: AAGATGTCCCTG AAGATGTCCCTG 0 5 2.585.11E−07 3′ss Br. 38570326-38572514 38570326-38572532 TGAGGATTGTGTTGAGGATTGCAC GTTTGTTTCCAC TGGGTGCAAGTT AGGC (224) CCTG (225) 115 chr6:chr6: AGAGAAGTCGTT AGAGAAGTCGTT 0 5 2.58 2.67E−07 3′ss Br.31919381-31919551 31919381-31919651 TCATTCAATCTG TCATTCAAGTTGATTCCTTTAGGT GTGTAATCAGCT CAGC (226) GGGG (52) 116 chrX: chrX:AGCCCAGCAGTT AGCCCAGCAGTT 0 5 2.58 5.15E−07 3′ss Br. 48751114-4875118248751100-48751182 CCGAAATGTCTC CCGAAATGCGCC CCTTCTCCAGCG CCCATTCCTGGACCCC (227) GGAC (228) 117 chr17: chr17: CCCTCCCCCGGC ACCCAAGCCTTG 2 162.50 3.35E−04 exon Br. 40714505-40714629 40714237-40714629 TCCTGTCGGCCTAGGTTTCAGCCT incl. GGGCAGCATGGC GGGCAGCATGGC CGTA (229) CGTA (18) 118chr15: chr15: TGATTCCAAGCA TGATTCCAAGCA 1 10 2.46 1.54E−06 3′ss Br.25213229-25219533 25213229-25219457 AAAACCAGCCTT AAAACCAGGCTCCCCCTAGGTCTT CATCTACTCTTT CAGA (230) GAAG (231) 119 chr2: chr2:CAAGTCCATCTC CAAGTCCATCTC 2 15 2.42 6.24E−03 3′ss Br.132288400-132289224 132288400-132289236 TAATTCAGCCAA TAATTCAGGCAACTCTCAAGGCAA GGCCAGGCCCCA GGCC (232) GCCC (98) 120 chr7: chr7:CTATCAAAAGAG CTATCAAAAGAG 2 15 2.42 9.00E−05 exon Br. 8267481-82682308261028-8268230 GATATGTTCATT GATATGTTTCTT incl. TTAGGAGGCCAAGTCTCAAGAAGA GGCA (233) AAAC (133) 121 chr3: chr3: GTCTTCCAATGGGTCTTCCAATGG 7 41 2.39 2.38E−07 3′ss Br. 148759467-148759952148759455-148759952 CCCCTCAGCCTT CCCCTCAGGAAA TTCTCTAGGAAA TGATACACCTGATGAT (234) AGAA (235) 122 chr8: chr8: GCACCTCCCCGG GCACCTCCCCGG 4 252.38 3.96E−02 exon Br. 144873910-144874045 144873610-144874045GACGCCTGCCCT GACGCCTGTCAC incl. TGTCTGGAAAGA CGGACTTTGCTG AGTT (236)AGGA (237) 123 chr17: chr17: TGGACCCCAGAC GTCCCGGAACCA 1 9 2.32 5.71E−03exon Br. 3828735-3831533 3828735-3831956 CACACCGGAAGA CATGCACGAAGA incl.AATGAGCCAGAA AATGAGCCAGAA GTGA (238) GTGA (239) 124 chr11: chr11:TCTGTGTTCCCA TGTATGACGTCA 0 4 2.32 2.08E−03 5′ss Br. 66040546-6604327466039931-66043274 TCGCACAGGAAT CTGACCAGGAAT CCTACGCCAACG CCTACGCCAACGTGAA (240) TGAA (241) 125 chr12: chr12: GGAATATGATCC GGAATATGATCC 0 42.32 6.10E−04 3′ss Br. 15272132-15273996 15264351-15273996 CACCCTCGTACTCACCCTCGAATC TCTCAAAGAGGA AACCTACCGACA TGGC (242) CCAA (243) 126 chr16:chr16: GAACTGGCACCG GAACTGGCACCG 0 4 2.32 1.02E−06 3′ss Br.313774-313996 313774-314014 ACAGACAGTGTC ACAGACAGATCC CCCTCCCTCCCCTGTTTCTGGACC AGAT (244) TTGG (245) 127 chr19: chr19: TGATGAAGACCTTGATGAAGACCT 0 4 2.32 1.48E−03 3′ss Br. 44116292-4411838044112259-44118380 TTCCCCAGATCT TTCCCCAGGCCC CTTAGGTGAAGA CGAGCATTCCTCCATG (246) TGAT (247) 128 chr1: chr1: CCAGGCCGACAT CCAGGCCGACAT 0 4 2.324.27E−07 3′ss Br. 228335400-228336058 228335400-228336071 GGAGAGCAGCCCGGAGAGCAGCAA CACCCACAGGCA GGAGCCCGGCCT AGGA (248) GTTT (249) 129 chr20:chr20: ACATGAAGGTGG ACATGAAGGTGG 0 4 2.32 5.15E−07 3′ss Br.34144042-34144761 34144042-34144743 ACGGAGAGTTCT ACGGAGAGGTACCTGTGACCAGAC TGAGGACAAATC ATGA (250) AGTT (50) 130 chr2: chr2:TTCGTCCATATG TTCGTCCATATG 0 4 2.32 2.38E−03 3′ss Br. 198267783-198268308198267759-198268308 TGCATAAGCTTC TGCATAAGATCC TTCTCTTTTCTC TCGTGGTCATTGTTTT (251) AACC (252) 131 chr3: chr3: AGGGATGGCCAG AGAAGGGAGCGA 0 4 2.328.01E−04 5′ss Br. 47969840-47981988 47969840-48019354 TGGTAGTGGGTCTACTACAGGGTC TCCAACTGAATT TCCAACTGAATT CCTT (253) CCTT (254) 132 chr4:chr4: CCAATGTGGTTC CCAATGTGGTTC 0 4 2.32 1.00E−05 3′ss Br.38907482-38910197 38907482-38910212 AAAACACATTAT AAAACACAGGTACTCATCTGCAGG AAAGTGTCTTAA GTAA (255) CTGG (256) 133 chr7: chr7:CCATTGATGCAA CCATTGATGCAA 0 4 2.32 7.45E−03 exon Br. 94227316-9422808694218044-94228086 ACGCAGCAATGG ACGCAGCAGAAC incl. AGTTTCGCTCCTTTGCCACATCAG GTTG (257) ACTC (258) 134 chr8: chr8: GCTGCATCTGGACAGTGTTAGTGA 0 4 2.32 6.84E−03 5′ss Br. 17873340-1788286917872349-17882869 GGTCCTGGGAAG ATGACTATGAAG CAGAATCTGGTA CAGAATCTGGTAATAT (259) ATAT (260) 135 chr17: chr17: ACAAGGACACAG ACAAGGACACAG 10 532.30 5.76E−06 3′ss Br. 73518592-73519333 73518292-73519333 AAAACAAGCCTTAAAACAAGCTGG CCCACACAGGCC AGCACCGCTGCA CTGC (261) CCTC (262) 136 chr16:chr16: AGCTCGGACCAA AGCTCGGACCAA 9 48 2.29 1.29E−03 3′ss Br.47495337-47497792 47495337-47497809 GCGCTCAGTTTT GCGCTCAGCTTAAAAATTGCTATA GCCTGCGACGCT GCTT (263) TATG (264) 137 chr6: chr6:AGGGGGCTCTTT AGGGGGCTCTTT 6 32 2.24 3.39E−03 3′ss Br. 91269953-9127134091269933-91271340 ATATAATGTTTG ATATAATGTGCT TGCCTTTCTTTC GCATGGTGCTGAGCAG (265) ACCA (266) 138 chr15: chr15: GCCCCCAACTGA GCCCCCAACTGA 2 132.22 4.76E−03 exon Br. 41130464-41130740 41128480-41130740 GAAGCTGGGCTGGAAGCTGGTGCC incl. GAGTGCTGTGGC CTTGGTGTGGTG ACAA (267) GAAG (268) 139chr17: chr17: GAACGAGATCTC AGTATCAGAAGG 4 21 2.14 6.40E−03 5′ss Br.2276080-2276246 2275782-2276246 ATCCCACTAACT ACAAAAAGAACT ACAAAGAGCTGGACAAAGAGCTGG AGCT (269) AGCT (270) 140 chr17: chr17: TGAAGGTCCAGGTGAAGGTCCAGG 8 35 2.00 4.45E−02 3′ss Br. 4885470-4886051 4885455-4886051GCATGGAGCCTG GCATGGAGTGTC TCTCCTGGCAGT TCTATGGCTGCT GTCT (271) ACGT(272) 141 chr16: chr16: GGCGGCCGCGCC GGCGGCCGCGCC 2 11 2.00 3.29E−02exon Br. 1728357-1733509 1728357-1735439 GGCTCCAGGAAA GGCTCCAGGGCC incl.TGGCAACTGCTG ATGAAGCCCCCA ACAG (273) GGAG (274) 142 chr11: chr11:CCTTCCAGCTAC CCTTCCAGCTAC 1 7 2.00 1.25E−04 3′ss Br. 2993509-29972532993473-2997253 ATCGAAACGCAT ATCGAAACTTTA GAGGATGTTGTA CCTAAAGCAGTA TTTC(275) AAAA (276) 143 chr10: chr10: CTTTTCTCTTCT GATGTGATGAAC 0 3 2.002.72E−03 5′ss Br. 69583150-69595149 69583150-69597691 TTTTATAGGTTGTATCTTCGGTTG AACAAATCCTGG AACAAATCCTGG CAGA (277) CAGA (278) 144 chr11:chr11: GCACTGGGCATT GCACTGGGCATT 0 3 2.00 1.28E−07 3′ss Br.66053068-66053171 66053007-66053171 CAGAAAAGTCTC CAGAAAAGGTTCTCTTCCTCACCC TCCCCGGAGGTG CTGC (279) CTGG (280) 145 chr11: chr11:CTGTCACAGGGG CTGTCACAGGGG 0 3 2.00 2.18E−03 3′ss Br. 77090454-7709093877090433-77090938 AGTTTACGTCTT AGTTTACGGGAA GCATGTCTCTCT TGCCAGAGCAGTTACA (281) GGGC (282) 146 chr12: chr12: GGGTGCAAAAGA GGGTGCAAAAGA 0 32.00 2.66E−07 3′ss Br. 57032980-57033763 57033091-57033763 TCCTGCAGCCATTCCTGCAGGACT TCCAGGTTGCTG ACAAATCCCTCC AGGT (283) AGGA (284) 147 chr12:chr12: GGCACCCCAAAA GGCACCCCAAAA 0 3 2.00 9.82E−07 3′ss Br.58109976-58110164 58109976-58110194 GATGGCAGATCA GATGGCAGGTGCGTCTCTCCCTGT GAGCCCGACCAA TCTC (285) GGAT (286) 148 chr17: chr17:GCATCTCAGCCC GCATCTCAGCCC 0 3 2.00 2.72E−07 3′ss Br. 16344444-1634467016344444-16344681 AAGAGAAGTTTC AAGAGAAGGTTA TTTGCAGGTTAT TATTCCCAGAGGATTC (287) ATGT (288) 149 chr1: chr1: CTTGCCTTCCCA CTTGCCTTCCCA 0 3 2.002.32E−04 3′ss Br. 154246074-154246225 154246074-154246249 TCCTCCTGCAAATCCTCCTGAACT CACCTGCCACCT TCCAGGTCCTGA TTCT (289) GTCA (290) 150 chr1:chr1: CTACACAGAGCT CTACACAGAGCT 0 3 2.00 8.14E−08 3′ss Br.32096333-32098095 32096443-32098095 GCAGCAAGGTGT GCAGCAAGCTCTGCACCCAGCTGC GTCCCAAATGGG AGGT (291) CTAC (292) 151 chr2: chr2:ACCTGTTACCAC ACCTGTTACCAC 0 3 2.00 1.17E−04 3′ss Br. 101622533-101635459101622533-101622811 TTTCAAAATTTC TTTCAAAAATCT TGTGCTAAACAG ACAGACAGTCAATGTT (293) TGTG (294) 152 chr2: chr2: AGACAAGGGATT AGACAAGGGATT 0 3 2.003.82E−06 3′ss Br. 26437445-26437921 26437430-26437921 GGTGGAAACATTGGTGGAAAAATT TTATTTTACAGA GACAGCGTATGC ATTG (295) CATG (296) 153 chr3:chr3: CAACGAGAACAA CAACGAGAACAA 0 3 2.00 2.29E−07 3′ss Br.101401353-101401614 101401336-101401614 GCTATCAGTTAC GCTATCAGGGCTTTTTACCCCACA GCTAAGGAAGCA GGGC (297) AAAA (298) 154 chr5: chr5:TCTATATCCCCT TCTATATCCCCT 0 3 2.00 1.27E−06 3′ss Br. 177576859-177577888177576839-177577888 CTAAGACGCACT CTAAGACGGACC TCTTTCCCCTCT TGGGTGCAGCCGGTAG (299) CAGG (300) 155 chr6: chr6: TGGAGCCAGTTA TGGAGCCAGTTA 0 3 2.009.28E−04 3′ss Br. 31506716-31506923 31506632-31506923 CTGGGCAGGTGTCTGGGCAGGTGT GTTTTTGTGACA CTGTACTGGTGA GTCA (301) TGTG (302) 156 chrX:chrX: AAAAGAAACTGA AAAAGAAACTGA 13 54 1.97 1.08E−05 3′ss Br.129771378-129790554 129771384-129790554 GGAATCAGTATC GGAATCAGCCTTACAGGCAGAAGC AGTATCACAGGC TCTG (303) AGAA (304) 157 chrX: chrX:CAGCACTAGGTT CAGCACTAGGTT 7 30 1.95 8.04E−04 exon Br.135758876-135761693 135760115-135761693 ATAAAGAGGAGT ATAAAGAGAGGA skipCTAGTAAAAGCC TGTCTTATATCT CTAA (305) TAAA (306) 158 chr6: chr6:GCCCCCGTTTTC GCCCCCGTTTTC 4 18 1.93 9.28E−05 3′ss Br. 31936315-3193639931936315-31936462 CTGCCCAGCCCT CTGCCCAGTACC TGTCCTCAGTGC TGAAGCTGCGGGACCC (307) AGCG (308) 159 chr2: chr2: GCCGCCGCCGCC CACCTTATGAAG 10 401.90 4.22E−03 5′ss Br. 97757449-97760437 97757449-97757599 GCCGCCAGGCTCTATAGCAGGCTC TGATGCTGGTGT TGATGCTGGTGT CTGG (309) CTGG (310) 160 chr19:chr19: AGTGGCAGTGGC AGTGGCAGTGGC 6 25 1.89 2.97E−03 3′ss Br.6731065-6731209 6731122-6731209 TGTACCAGCCCA TGTACCAGCTCT CAGGAAACAACCTGGTGGAGGGCT CGTA (311) CCAC (312) 161 chr16: chr16: GAGATTCTGAAGGAGATTCTGAAG 4 16 1.77 5.02E−05 3′ss Br. 54954250-5495749654954322-54957496 ATAAGGAGTTCT ATAAGGAGGTAA CTTGTAGGATGC AACCTGTTTAGACACT (313) AATT (314) 162 chr2: chr2: CCAAGAGACAGC CCCCTGAGATGA 4 161.77 3.39E−06 exon Br. 27260760-27261013 27260570-27261013 ACATTCAGCTCCAGAAAGAGCTCC incl. TGAGCAGCCTGA TGAGCAGCCTGA CTGA (315) CTGA (184) 163chr10: chr10: TCAGAGCAGTCG CTACGACAGTGA 10 35 1.71 1.55E−02 5′ss Br.75290593-75294357 75290593-75296026 GGACACAGGACA AGATTCAGGACACCTGACTGATAG CCTGACTGATAG TGAA (316) TGAA (317) 164 chr1: chr1:CTGTTGTGTCCG CTGTTGTGTCCG 19 63 1.68 5.06E−05 3′ss Br.155278867-155279833 155278867-155279854 TTTTGAAGAGCC TTTTGAAGAATGCTTTGCTCCTCC AACGGAGACCAG CTCA (318) AATT (319) 165 chr16: chr16:CCGGCCCTACAG CCCTCCGCCTCC 6 21 1.65 3.26E−02 exon Br. 630972-632882632309-632882 GCTGGCGGATAA TGATGCAGATAA skip ACCCACTGCCCT ACCCACTGCCCTACAG (320) ACAG (321) 166 chr16: chr16: GAGATTCTGAAG GAGATTCTGAAG 18 571.61 6.30E−07 3′ss Br. 54954239-54957496 54954322-54957496 ATAAGGAGGATGATAAGGAGGTAA CCACTGGAAATG AACCTGTTTAGA TTGA (322) AATT (314) 167 chr14:chr14: TGAAAAGTCCAG TCCTGGAGGAGC 15 47 1.58 1.41E−02 5′ss Br.39734625-39746137 39736726-39746137 AGGAAGAGGTTG TACGCAGGGTTGTGGCAGCACTGC TGGCAGCACTGC CTGA (323) CTGA (324) 168 chr13: chr13:GTCATGGCAGAA CTATAGCTACTG 10 32 1.58 1.25E−02 exon Br. 21157158-2116510521164006-21165105 GACCTCCATCCA GATATGGGTCCA skip AGACATCTCTGGAGACATCTCTGG CATC (325) CATC (326) 169 chr17: chr17: CCGGAGCCCCTTCCGGAGCCCCTT 5 17 1.58 4.45E−02 3′ss Br. 45229302-4523203745229284-45232037 CAAAAAAGACTT CAAAAAAGTCTG TTCGTGTTTTAC TTGCCAGAATCGAGTC (327) GCCA (328) 170 chr16: chr16: CCACAGATACTA CCACAGATACTA 3 111.58 1.99E−02 3′ss Br. 47484364-47485306 47462809-47485306 TTAGGAGGCCATTTAGGAGGGAAT ACCACCCTGAAC TTATCATGGCAT GCGC (329) CCAG (330) 171 chr12:chr12: TGTTCAAGTTCC CCTGGTCGCAGT 1 5 1.58 1.50E−04 exon Br.57493873-57494628 57493873-57496072 CAAAGCAGGAGA TCAACAAGGAGA incl.TCCTGCTGGGCC TCCTGCTGGGCC GTGG (331) GTGG (215) 172 chr16: chr16:ACTCCCAGCTCA ACTCCCAGCTCA 0 2 1.58 6.10E−05 3′ss Br. 56403209-5641983056403239-56419830 ATGCAATGGTTC ATGCAATGGCTC CATACCATCTGG ATCAGATTCAAGTACT (332) AGAT (333) 173 chr17: chr17: ATCACTGTGACT ATCACTGTGACT 0 21.58 4.98E−05 3′ss Br. 80013701-80013861 80013701-80013876 TCCCTGAGGTCTTCCCTGAGCTGC CTGCTCCTCAGC TGTCCCCCAGCA TGCT (334) ACGT (335) 174 chr18:chr18: ATCCTCTCAATC ATCCTCTCAATC 0 2 1.58 4.76E−02 3′ss Br.51729496-51731367 51715381-51731367 AAAATAAGTTTG AAAATAAGGGTATGTGCACTTTTC AACCAGACTTGA TGCT (336) ATAC (337) 175 chr1: chr1:CTATTCCTTTAT CTATTCCTTTAT 0 2 1.58 5.34E−04 3′ss Br. 145109684-145112354145109684-145112372 TGAATTTGTTTT TGAATTTGATAC CTTCATCATTCT TTTCATTCAGAAAGAT (338) AACC (339) 176 chr2: chr2: AGTCATACCTGG AGTCATACCTGG 0 2 1.583.46E−03 3′ss Br. 242274627-242275373 242274627-242275389 AGCAGCAGTTTGAGCAGCAGAAAA TTTCTTTTCTAG AATTGAAAGAAC AAAA (340) TGTC (341) 177 chr3:chr3: GCAACCAGTTTG GCAACCAGTTTG 0 2 1.58 1.37E−04 3′ss Br.49395199-49395459 49395180-49395459 GGCATCAGCTGC GGCATCAGGAGACCTTCTCTCCTG ACGCCAAGAACG TAGG (342) AAGA (343) 178 chr4: chr4:CCATGGTCAAAA CCATGGTCAAAA 0 2 1.58 3.60E−05 3′ss Br. 152022314-152024139152022314-152024022 AATGGCAGCACC AATGGCAGACAA AACAGGTCCGCC TGATTGAAGCTCAAAT (344) ACGT (345) 179 chr5: chr5: GCCTGATGCCCG GCCTGATGCCCG 0 2 1.581.29E−02 exon Br. 1323984-1325865 1324928-1325865 AATTTCAGGCCAAATTTCAGTTTG skip TGAAGTACTTGT GCACTTACAGCG CATA (346) AATC (347) 180chr5: chr5: AGATTGAAGCTA AGATTGAAGCTA 0 2 1.58 6.18E−06 3′ss Br.132439718-132439902 132439718-132439924 AAATTAAGTTTT AAATTAAGGAGCCTGTCTTACCCA TGACAAGTACTT TTCC (348) GTAG (349) 181 chr5: chr5:AGCACAAGCTAT AGCACAAGCTAT 0 2 1.58 5.76E−06 3′ss Br. 44813384-4481499644813384-44815014 GTATCAAGCATA GTATCAAGGATT ACTTTCTTCTAC CTGGAGTGAAGCAGGA (350) AGAT (351) 182 chr6: chr6: AGATGTAAAAGT AGATGTAAAAGT 0 2 1.585.43E−04 3′ss Br. 52546712-52548863 52546712-52548875 GTCACTGTTTTGGTCACTGTTTAC GTTTTCAGTTAC AGCTTTCTTCCT AGCT (352) GGCT (353) 183 chr7:chr7: CTGCAGCCTCCG CCATTGATGCAA 0 2 1.58 8.78E−03 exon Br.94218044-94227241 94218044-94228086 CCTCCCAGGAAC ACGCAGCAGAAC incl.TTGCCACATCAG TTGCCACATCAG ACTC (354) ACTC (258) 184 chr15: chr15:AGGATGATGCAG AGGATGATGCAG 10 28 1.40 1.70E−03 3′ss Br. 59373483-5937630059373483-59376327 CATCCAACTGGT CATCCAACGCGG CTTTTTGTGTTC GCACATGAACGCTGTG (355) CCCC (356) 185 chr1: chr1: TGGTGAAATGGA TGGTGAAATGGA 12 331.39 1.25E−03 3′ss Br. 153925126-153925280 153925111-153925280CCCCAAAGTCTT CCCCAAAGTACC TCTCTTTCAAGT TGCTATTGAGGA ACCT (357) GAAC(358) 186 chr1: chr1: AGCTTAAAGAAC GATCAAGGCAAC 9 25 1.38 3.31E−02 exonBr. 151739775-151742647 151740709-151742647 TGTATTCGTTTG CGGGAAAGTTTGskip ACTGCAACCCTG ACTGCAACCCTG GAGT (359) GAGT (360) 187 chr19: chr19:AACACACCAACT AACACACCAACT 1 4 1.32 8.52E−04 3′ss Br. 47342877-4734924947342835-47349249 TTGTGGAGGTCC TTGTGGAGTTCC TGGCAATCTCCG GGAACTTTAAGATTGC (361) TCAT (362) 188 chr15: chr15: GCGGGTCTGCAG GTTCCAGGTCCT 5 131.22 5.55E−04 exon Br. 75631685-75632305 75632219-75632305 CCTACGCAAACTCCTGGCAGAACT skip GAAGCAGGCCCA GAAGCAGGCCCA GACC (363) GACC (364) 189chr1: chr1: CCCGCTGCCCCA ATTCTGATATAG 5 13 1.22 1.52E−02 exon Br.212459633-212506838 212502673-212506838 GCTCAAAGATCA TAAAAATGATCA skipGTGCTAACATCT GTGCTAACATCT TCCG (365) TCCG (366) 190 chr22: chr22:ATGAGTTTCCCA ATGAGTTTCCCA 2 6 1.22 1.59E−03 3′ss Br. 30976673-3097699830976688-30976998 CCGATGGGGAGG CCGATGGGGAGA AAGACCGCAGGA TGTCAGCGCAGGAGGA (367) AGGA (368) 191 chr7: chr7: AGTTTATTTAAC AGTTTATTTAAC 2 6 1.223.40E−02 exon Br. 80535232-80545994 80458061-80545994 ATTTGATGAGCCATTTGATGAACT incl. TACCTTGTACAA TCGAGAAACCAA TGCT (369) GACC (370) 192chr8: chr8: CCACCTAGCAGC CCACCTAGCAGC 2 6 1.22 1.17E−03 intron Br.145153766-145153768 145153691-145153768 CACCAGAGACCA CACCAGAGGTTA reten-GAGGTGGCACAG CAAGGGGAGAGT tion GCAG (371) GGCC (372) 193 chr9: chr9:TCCAGGATCCTG GGCAGCGGAGGG 2 6 1.22 8.61E−03 exon Br. 96285645-9628943696278551-96289436 AGGCATGGCCAT GCGACAAACCAT incl. ATCAGCGGGAACATCAGCGGGAAC AAGA (373) AAGA (374) 194 chr2: chr2: GGCAACTTCGTTGGCAACTTCGTT 20 47 1.19 5.26E−03 3′ss Br. 106781255-106782511106781240-106782511 AATATGAGCTTT AATATGAGGTCT CTACTCAACAGG ATCCAGGAAAATTCTA (375) GGTG (376) 195 chr19: chr19: GGAGCCTGGGCA GGAGCCTGGGCA 6 151.19 1.98E−02 3′ss Br. 7976215-7976299 7976215-7976320 TCTCGTTGCCCTTCTCGTTGGTGG GCCCGTCTCCCT AGCTGGCAACAG CCCA (377) GACA (378) 196 chr11:chr11: CTGGTGTGCTTG CTGGTGTGCTTG 3 8 1.17 4.87E−02 exon Br.9161795-9163486 9161401-9163486 GGAGCCAGGGTT GGAGCCAGAGAT incl.ATCATGAAGATT CACCTCCTACAC AAAT (379) CACT (380) 197 chr1: chr1:ATTGGAGGAGCT ATTGGAGGAGCT 10 23 1.13 3.12E−03 exon Br.160252899-160254844 160253429-160254844 TCTGGAAAGATG TCTGGAAAGTGC skipCCCTCTTCGCTT TCTTGATGATTT CCCA (381) CGAT (382) 198 chr19: chr19:AATGACGTGCTG AATGACGTGCTG 7 16 1.09 1.69E−02 3′ss Br. 16641724-1664340816641691-16643408 CACCACTGGGCC CACCACTGCCAG CTGACGCGCGGA CGCAAGCAGGCCAAGT (383) CGGG (384) 199 chr3: chr3: GCCTGGGGTGGA GCCTGGGGTGGA 9 201.07 3.01E−02 exon Br. 39141945-39142237 39141994-39142237 GAGGGCAGCCCCGAGGGCAGTCTG skip CCAGCTACCACA GGATGTGGCATT AGAA (385) GGCT (386) 200chr2: chr2: GGAAATGGGACA GGAAATGGGACA 11 24 1.06 3.05E−03 3′ss Br.230657846-230659894 230657861-230659894 GGAGGCAGAGGA GGAGGCAGCTTTTCACAGGCTTTA TCTCTCAACAGA AAAT (387) GGAT (388) 201 chr10: chr10:AGACCGACTGCC AGACCGACTGCC 5 11 1.00 2.09E−02 exon Br.123718925-123719872 123719110-123719872 AGTAATAGGAGA AGTAATAGAGCC skipTTGTGAAGACCT TGTTAGTATTAA TTGA (389) TGAA (390) 202 chr1: chr1:TCATGCTAGCCG TCATGCTAGCCG 5 11 1.00 3.31E−02 exon Br. 44064584-4406774144064584-44069086 AGGCCCAGTGGC AGGCCCAGGAAA incl. GGCCAGAGGAGTCCACTATCAGCG CCGA (391) GCCT (392) 203 chr1: chr1: GAAGGCAGCTGAGAAGGCAGCTGA 4 9 1.00 1.37E−03 3′ss Br. 11131045-1113214311131030-11132143 GCAAACAGTTCT GCAAACAGCTGC CTCCCTTGCAGC CCGGGAACAGGCTGCC (393) AAAG (394) 204 chr6: chr6: GCCAACAGCCAA GCCAACAGCCAA 3 7 1.006.32E−03 exon Br. 109690220-109697276 109691670-109697276 TTCTACAGGTACTTCTACAGCTAA skip AACAAATAACAC ACCCACAGTTCA TGTG (395) GCCC (396) 205chr17: chr17: CCCATCAACTGC CCCATCAACTGC 2 5 1.00 4.46E−02 exon Br.37873733-37879571 37873733-37876039 ACCCACTCCCCT ACCCACTCCTGT skipCTGACGTCCATC GTGGACCTGGAT ATCT (397) GACA (398) 206 chr17: chr17:GCGGAAAGAATT GCGGAAAGAATT 2 5 1.00 4.49E−02 3′ss Br. 5250220-52537665250220-5253745 GCATGAAGAGCG GCATGAAGTTTG ACAACAACACAA CCATCTCTTGGA CCAG(399) GCAA (400) 207 chr1: chr1: TGTGGGAATTAC AAGAAGGGATGG 2 5 1.007.58E−03 exon Br. 27260910-27267947 27250657-27267947 AATTCAAGCTTACAGAGAAGCTTA incl. TCACACAGACTT TCACACAGACTT TCAG (401) TCAG (402) 208chr5: chr5: CTTCCTCAAGTC CTTCCTCAAGTC 1 3 1.00 1.35E−02 3′ss Br.176759270-176761284 176759247-176761284 GCCCAAAGCTCC GCCCAAAGACAACCCGTTTCTTCT CGTGGACGACCC CCCC (403) CACG (404) 209 chr7: chr7:TCTTCGCTGGTG TCTTCGCTGGTG 1 3 1.00 8.43E−03 exon Br. 44619227-4462104744620838-44621047 GCAAACTGTATC GCAAACTGCGGG skip GTGAAGAGCGCTTGCATCTCGACA TCCG (405) TCCA (406) 210 chr1: chr1: GCAAGAAGTACAGCAAGAAGTACA 0 1 1.00 9.69E−03 3′ss Br. 165619201-165620230165619201-165620250 AAGTGGAGTATG AAGTGGAGTATC TGCTTTGTTGTG CTATCATGTACAACAG (407) GCAC (408) 211 chr3: chr3: TGTAGGAGCAAT TGTAGGAGCAAT 0 1 1.002.54E−04 3′ss Br. 42826828-42827519 42826812-42827519 GACTGTTGCATTGACTGTTGGTAT CTTTTTCTTTAG GGGCTATTCCAT GTAT (409) GTAT (410) 212 chr8:chr8: CCTTCCTGGATC AAGTGCAGATAG 0 1 1.00 5.33E−04 exon Br.117738411-117746515 117738411-117767904 CCCCTAAGGTGG ATGGCCTTGTGG incl.TATTAAAGATAA TATTAAAGATAA TCAA (411) TCAA (412) 213 chrX: chrX:CAGGTCTAACTC CAGGTCTAACTC 0 1 1.00 1.53E−02 3′ss Br. 54835809-5483655054835809-54836154 GCTTCCAGGCCC GCTTCCAGGCTG CAGCAGATGAAC AAGCTTCAGAAACTGA (413) AGGA (414) 214 chr16: chr16: CCTCCCCATACC GCCTGCCCCGGA 10 200.93 3.40E−02 exon Br. 30012361-30016541 30012851-30016541 TGAGCTCGATGGAACTCAAGATGG skip CGGTGGGACCCC CGGTGGGACCCC CCGA (415) CCGA (82) 215chr6: chr6: GCAAAAGGATAT GCAAAAGGATAT 10 20 0.93 2.78E−02 3′ss Br.43006222-43006303 43006210-43006303 ACCAGGAGCATT ACCAGGAGGGGTTATTTCAGGGGT CCTCAAGATTCG CCTC (416) AGAT (417) 216 chr6: chr6:CACTCCAATTTA CACTCCAATTTA 9 18 0.93 1.40E−02 exon Br.135517140-135518098 135517140-135520045 TAGATTCTGATT TAGATTCTTTCT incl.CTTCATCATGGT TAAACACTTCCA GTGA (418) GTAA (419) 217 chr7: chr7:TGAGAGTCTTCA TGAGAGTCTTCA 45 85 0.90 3.07E−04 3′ss Br. 99943591-9994733999943591-99947421 GTTACTAGTTTG GTTACTAGAGGC TCTTTCCTAGAT GGATTTCCCTGACCAG (420) CTGA (421) 218 chr12: chr12: TTAACAGCATTT CCCAGTCATTCA 10 190.86 1.21E−02 intron Br. 111085013-111085015 111082934-111085015TGTTTTGCGATT ACAGGAAGGATT reten- CCTGCCAGCTCC CCTGCCAGCTCC tion CAGG(422) CAGG (423) 219 chr4: chr4: GATGAATGCTGA GATGAATGCTGA 4 8 0.852.40E−02 exon Br. 141300346-141302115 141300346-141300722 CATGGATGATCTCATGGATGCAGT skip CTCTGCAAGAGT TGATGCTGAAAA AGAT (424) TCAA (425) 220chr10: chr10: GTCAATGCTTCC GTCAATGCTTCC 18 33 0.84 3.71E−02 3′ss Br.114905856-114910741 114905856-114910756 ATGTCCAGCTTT ATGTCCAGGTTCCTGTCTTCTAGG CCTCCCCATATG TTCC (426) GTCC (427) 221 chr16: chr16:TATGGCAAGGAG TATGGCAAGGAG 7 13 0.81 2.25E−02 3′ss Br. 30767593-3076767530767593-30767687 GTCGACCTTCTC GTCGACCTCTGG TTTCCCAGCTGG GCCTGTGGGGTGGCCT (428) ATCT (429) 222 chr3: chr3: TGGTTTTACCTC TGGTTTTACCTC 7 130.81 5.98E−03 3′ss Br. 128890351-128890476 128890381-128890476GGATAGAGACAT GGATAGAGGTTT TTGTTATCGCTG CCAGTTTGTTTC TGGT (430) CTCG(431) 223 chr1: chr1: GAATCCGTATCT GAATCCGTATCT 34 60 0.80 2.74E−04 3′ssBr. 155278756-155279833 155278756-155279854 GGGAACAGAGCC GGGAACAGAATGCTTTGCTCCTCC AACGGAGACCAG CTCA (432) AATT (433) 224 chr20: chr20:TCCAGGAGTTCC TTTGACTAGGGT 22 39 0.80 1.59E−02 exon Br. 264722-270899264722-270199 AGGTTCCGTGTT CCAACCAGTGTT skip TCACTTCAAGCC TCACTTCAAGCCCACT (434) CACT (435) 225 chr1: chr1: GGGCCTGATGAA GGGCCTGATGAA 30 520.77 2.84E−03 exon Br. 53370762-53373539 53372283-53373539 TGACATCGCTTCTGACATCGCAGC skip CTCGGCAGTCAT CTTCCCTGCACC GGGA (436) CACC (437) 226chr4: chr4: AGCCCCAGGATG AGCCCCAGGATG 16 28 0.77 1.45E−02 exon Br.5815889-5825343 5815889-5819937 CCTCGCAGCTCT CCTCGCAGACGT skipCGGAAGAACTGG GCCTTCTGCCAT TTGT (438) GATT (439) 227 chr20: chr20:ACTTGCCTGTGA ACTTGCCTGTGA 15 26 0.75 1.83E−03 3′ss Br. 47741142-4775236947741124-47752369 ATTTCGAGTCTT ATTTCGAGGTGG TCCCTCTGAAAC CCCGGGAGAGTGAGGT (440) GCCC (441) 228 chrX: chrX: TACCCGGGACAA TACCCGGGACAA 2 4 0.744.57E−02 3′ss Br. 48933637-48934088 48933604-48934088 CCCCAAGGCCGCCCCCAAGGGGCT CCACCCCACCCC CTGTGACCTCTG CCAT (442) CCCC (443) 229 chr1:chr1: CATAGTGGAAGT CATAGTGGAAGT 39 64 0.70 4.20E−07 3′ss Br.67890660-67890765 67890642-67890765 GATAGATCTTCT GATAGATCTGGCTTTTCACATTAC CTGAAGCACGAG AGTG (444) GACA (445) 230 chr1: chr1:GCTGTACCTTCA GCTGTACCTTCA 18 29 0.66 2.84E−03 3′ss Br.156705701-156706410 156705701-156706423 GGAACAGGCCCT GGAACAGGGTTTTTCTCCCAGGTT CCATGCTGAGCT TCCA (446) CCTG (447) 231 chr10: chr10:TAAAGCGACTCA TAAAGCGACTCA 29 46 0.65 1.78E−02 exon Br.101507147-101514285 101507147-101510125 TTGAGCAGGAGG TTGAGCAGGCAA skipTGGTATAACAGA AAGGCAGGATTG CAGA (448) TGGT (449) 232 chr12: chr12:TGGGAATCTGGC TGGGAATCTGGC 31 49 0.64 3.09E−04 3′ss Br.117595889-117603289 117595868-117603289 CAGAGAAGTCTT CAGAGAAGGTGCTCTGTCTTGTTT TTGACATCCTCC TGAA (450) AGCA (451) 233 chr2: chr2:AGAAAACATCGA AGAAAACATCGA 8 13 0.64 2.66E−02 exon Br.114472772-114476730 114475427-114476730 ATTCAGAGCTTG ATTCAGAGAGTT skipATAATGGAACTA CCAGAAGACAGC TACA (452) GAAC (453) 234 chr11: chr11:CGTCCGCCAGTC AGCCGGGCGTTG 34 53 0.63 1.78E−02 5′ss Br. 504996-507112504996-506608 GTCCCGAGGCAT GGGGAAAGGCAT GAAGAACTCTTG GAAGAACTCTTG ACTG(454) ACTG (455) 235 chrX: chrX: ACTAATCTTCAG CAAACACCTCTT 14 22 0.622.22E−04 exon Br. 123224814-123227867 123224614-123227867 CATGCCATTCGGGATTATAATCGG incl. CGTGGCACAAGC CGTGGCACAAGC CTAA (456) CTAA (457) 236chr9: chr9: CACCACAAAATC CACCACAAAATC 37 57 0.61 6.00E−04 3′ss Br.140622981-140637822 140622981-140637843 ACAGACAGCTTG ACAGACAGCAGCCTTGCCTTTTGT TGCAGTATCTCG TTTA (458) GAAG (459) 237 chr2: chr2:CTCCTACTACAC AGAGCTCAAAGA 34 52 0.60 2.66E−02 exon Br.152324660-152325154 152325065-152325154 AATCTAAGATTT AGTGTTTAATTT skipCAGAAATGGCCA CAGAAATGGCCA AAGA (460) AAGA (461) 238 chr12: chr12:ATTTCCAGAGGA ATTTCCAGAGGA 49 74 0.58 1.10E−04 3′ss Br. 95660408-9566381495660408-95663826 TTTACACTTTTG TTTACACTGGTC CTTGACAGGGTC AGTGCTGCTTGCAGTG (462) CCAT (463) 239 chr7: chr7: GAGTCGGCGCCG CACAGAGAGCTG 5 8 0.584.45E−02 exon Br. 44880611-44887567 44880611-44882875 AGAACATGTTTCGGCTACAGTTTC skip CTGTGGGCCGCA CTGTGGGCCGCA TCCA (464) TCCA (465) 240chr10: chr10: TGACGTTCTCTG TGACGTTCTCTG 46 68 0.55 4.09E−04 3′ss Br.75554088-75554298 75554088-75554313 TGCTCCAGTGGT TGCTCCAGGTTCTTCTCCCACAGG CCGGCCCCCAAG TTCC (466) TCGC (467) 241 chrX: chrX:CAAACACCTCTT CAAACACCTCTT 14 21 0.55 2.21E−02 exon Br.123224614-123224703 123224614-123227867 GATTATAACACG GATTATAATCGG incl.CAGGTAACATGG CGTGGCACAAGC ATGT (468) CTAA (457) 242 chr2: chr2:TACTCCAGCTTC TACTCCAGCTTC 30 44 0.54 8.18E−03 3′ss Br. 86398468-8640077286398435-86400772 AGCAACAGCACC AGCAACAGCAGG TACAGAAGCGGC TGATACCCTGTCTCAA (469) GGTC (470) 243 chr17: chr17: TCTCAGCTGACG GGCATGCAACCA 13 190.51 4.21E−03 exon Br. 47882807-47888837 47886570-47888837 AATGCAAGGCACGGCACCAGGCAC skip CAACGGAGAGAC CAACGGAGAGAC AGCT (471) AGCT (472) 244chr1: chr1: TCAAATCATTTA TCAAATCATTTA 9 13 0.49 3.77E−02 3′ss Br.109743522-109745534 109743522-109745565 CCTCCAAGCAGC CCTCCAAGAGGACAGCTCCTGTCA CTCCTGATGGAT CCAT (473) TTGA (474) 245 chr11: chr11:AGCAAAAAGGGG AGCAAAAAGGGG 35 49 0.47 2.40E−02 3′ss Br. 502249-504823502181-504823 TGTCTCAGAATC TGTCTCAGGCCA TCCGGCCTGTGA CTCTTCACCTCC AACT(475) ACCA (476) 246 chr6: chr6: TGTTGCCTCCGC TGGTCATGGCCA 44 60 0.445.91E−04 exon Br. 31611971-31612083 31611971-31612301 GGCCGCAGGACAAACCCTGGGACA incl. GCAGGTGCCAGG GCAGGTGCCAGG CTTC (477) CTTC (478) 247chr20: chr20: TGCCTAAGGCGG TGCCTAAGGCGG 63 84 0.41 4.16E−05 3′ss Br.30310151-30310420 30310133-30310420 ATTTGAATCTCT ATTTGAATAATCTTCTCTCCCTTC TTATCTTGGCTT AGAA (479) TGGA (480) 248 chr6: chr6:TGGTCATGGCCA TGGTCATGGCCA 51 68 0.41 4.27E−03 exon Br. 31612191-3161230131611971-31612301 AACCCTGGGCTC AACCCTGGGACA incl. CACCCTCATCCAGCAGGTGCCAGG GCTG (481) CTTC (478) 249 chr10: chr10: TGCAGATTCCAACCTTCCACCCAA 49 63 0.36 4.56E−02 exon Br. 34649187-3466142534649187-34663801 AAGAAACGAAAG GGGAACTGAAAG incl. CAGAAGATGAGGCAGAAGATGAGG ATAT (482) ATAT (483) 250 chr4: chr4: AGGAGGGCCCCCAGGAGGGCCCCC 43 54 0.32 1.35E−02 3′ss Br. 860289-860743 860322-860743TGCCGCTGGCAA TGCCGCTGCTGA CAACTCCCAGCC CCCCTTTGGCCC CTGC (484) GCTT(485) 251 chr8: chr8: AACAACTGCCCA AACAACTGCCCA 3 4 0.32 4.44E−02 3′ssBr. 99054946-99057170 99055003-99057170 GCTTTGAGTGGC GCTTTGAGGAAAAATAATATTGAA TCTGAAATAGAG CTGG (486) TACT (487) 252 chr8: chr8:GTTGTGCCCATG GTTGTGCCCATG 66 81 0.29 4.37E−02 exon Br. 48694815-4869493848691654-48694938 ACCTCCAGGTTA ACCTCCAGTGAT incl. GGATTAATTGAGCCCAGGGCACCG TGGC (488) CCGT (489) 253 chr20: chr20: GTTAATGGGTTTGTTAATGGGTTT 57 68 0.25 2.24E−02 exon Br. 57470739-5747399557470739-57478585 AATGGAGAGGGC AATGGAGATGAG incl. GGCGAAGAGGACAAGGCAACCAAA CCGC (490) GTGC (491) 254 chr20: chr20: GCAAGGAGCAACGTTAATGGGTTT 59 69 0.22 4.34E−03 exon Br. 57474040-5747858557470739-57478585 AGCGATGGTGAG AATGGAGATGAG incl. AAGGCAACCAAAAAGGCAACCAAA GTGC (492) GTGC (491) 255 chr19: chr19: AGTTTGAGATGAAGTTTGAGATGA 79 91 0.20 2.28E−02 exon Br. 17339118-1733961117339118-17339817 AGCGAATGGATC AGCGAATGCTCC incl. CTGGCTTCCTGGCCCTACCAGGGG ACAA (493) TCGC (494) 256 chrX: chrX: AGAAACCTTGAAAGAAACCTTGAA 84 95 0.18 4.29E−02 exon Br. 2209644-23267852310515-2326785 CGACAAAGTGGA CGACAAAGAGAC skip ATTTTTATACTG GTGAGTCTTGCTTGAC (495) GTGT (496) 257 chrY: chrY: AGAAACCTTGAA AGAAACCTTGAA 84 950.18 4.29E−02 exon Br. 2159644-2276785 2260515-2276785 CGACAAAGTGGACGACAAAGAGAC skip ATTTTTATACTG GTGAGTCTTGCT TGAC (495) GTGT (496) 258chr11: chr11: ACCCCTTTGGCA ACCCCTTTGGCA 0 60 5.93 5.12E−05 3′ss CLL67815439-67815553 67815439-67816345 TCGATCCTGCCC TCGATCCTATTTTTTCCTCAGCAC GGAGCCTGGCTG AAGA (497) CCAA (498) 259 chr2: chr2:TGGGAGGAGCAT TGGGAGGAGCAT 0 59 5.91 7.08E−07 3′ss CLL 97285513-9729704897285499-97297048 GTCAACAGAGTT GTCAACAGGACT TCCCTTATAGGA GGCTGGACAATGCTGG (9) GCCC (10) 260 chr10: chr10: TAAAGTGTTGGC TAAAGTGTTGGC 0 51 5.705.10E−07 3′ss CLL 93244412-93244921 93244412-93244936 TTTACTTAAATTTTTACTTAATAC TATCTTTACAGA TGCAAACAATTT TACT (499) AGTT (500) 261 chr21:chr21: ACCTCGTCAGAA ACCTCGTCAGAA 0 48 5.61 2.38E−05 3′ss CLL47970657-47971529 47970657-47971546 ACAACCAGAGTT ACAACCAGAGGTCCCCCGTTTCTA TGGACCAGCCTC GAGG (501) AATG (502) 262 chr22: chr22:TCATCCAGAGCC TCATCCAGAGCC 0 48 5.61 3.58E−03 3′ss CLL 50966161-5096694050966146-50966940 CAGAGCAGGGGA CAGAGCAGATGC TGTCTGACCAGA AAGTGCTGCTGGTGCA (173) ACCA (174) 263 chr13: chr13: AAAGATTTCAGA AAAGATTTCAGA 0 395.32 1.50E−02 3′ss CLL 26970491-26971275 26970491-26971289 AGAAATACTATTAGAAATACGTAT TCTCTTTCAGGT ACCAACTGCAGC ATAC (503) CTTA (504) 264 chr5:chr5: CCAAAAGAGGGG CTCCATGCTCAG 0 39 5.32 4.28E−05 exon CLL865696-869359 865696-870587 ATAATGAGGGAA CTCTCTGGGGAA incl. GGTGAAGAAGGAGGTGAAGAAGGA GCTG (505) GCTG (129) 265 chr22: chr22: CTCTCTCCAACCCTCTCTCCAACC 0 38 5.29 4.92E−04 3′ss CLL 39064137-3906687439064137-39066888 TGCATTCTCATC TGCATTCTTTGG TCGCCCACAGTT ATCGATCAACCCGGAT (140) GGGA (141) 266 chr10: chr10: TCATCTTGAAAA TCATCTTGAAAA 0 345.13 3.62E−05 3′ss CLL 89519557-89527429 89516679-89527429 ATGAAAATTCCTATGAAAATGTGG ATTTTACAGCTG ATAGGCATGTAG AGGA (506) ACCT (507) 267 chr20:chr20: TTTGCAGGGAAT TTTGCAGGGAAT 0 34 5.13 3.01E−05 3′ss CLL35282126-35284762 35282104-35284762 GGGCTACATCCC GGGCTACATACCCTTGGTTCTCTG ATCTGCCAGCAT TTAC (35) GACT (36) 268 chr10: chr10:ACCCTGTCTACC ACCCTGTCTACC 1 64 5.02 4.28E−05 3′ss CLL102276734-102286155 102276717-102286155 AGCCTGTGTTTT AGCCTGTGGATACTGCCACCTACA GACCATGAAGCT GGAT (508) GAAG (509) 269 chr14: chr14:AGATGTCAGGTG AGATGTCAGGTG 1 62 4.98 8.04E−09 3′ss CLL 75356052-7535658075356052-75356599 GGAGAAAGCCTT GGAGAAAGCTGT TGATTGTCTTTT TGGAGACACAGTCAGC (89) TGCA (90) 270 chr19: chr19: TGACACAGCCCT TGACACAGCCCT 1 594.91 4.19E−04 3′ss CLL 16264018-16265147 16264018-16265208 GCAGGCAGGGTCGCAGGCAGAAGG CGTGCAGGACCT ATCCCGCAAACG TTCC (510) TGGA (511) 271 chr7:chr7: GCGGGGCGAGGG GCGGGGCGAGGG 1 59 4.91 8.04E−09 3′ss CLL102074108-102076648 102074108-102076671 CAGCTCCGCGTT CAGCTCCGGGAATCTCTGAATTCT GGAACGTCCCAG CCCC (512) GGAT (513) 272 chr1: chr1:TCTTTGGAAAAT TCTTTGGAAAAT 0 29 4.91 3.49E−03 3′ss CLL101458310-101460665 101458296-101460665 CTAATCAATTTT CTAATCAAGGGACTGCCTATAGGG AGGAAGATCTAT GAAG (25) GAAC (26) 273 chr7: chr7:CCACCTCACCAT CCACCTCACCAT 0 29 4.91 1.26E−02 3′ss CLL 99954506-9995584999954506-99955842 CACCCAGGGCAG CACCCAGGCCCT CCCCTCCACAGG CAGGCAGCCCCTGCCC (514) CCAC (515) 274 chr19: chr19: GATGGTGGATGA GATGGTGGATGA 1 574.86 7.10E−04 3′ss CLL 23545541-23556543 23545527-23556543 ACCCACAGTTTTACCCACAGGTAT TTTTTTTCAGGT ATGTCCTCATTT ATAT (11) TCCT (12) 275 chr3:chr3: GCCAACCTAGAG GCCAACCTAGAG 1 56 4.83 2.18E−05 3′ss CLL108403188-108405274 108403188-108405291 CCCCCCTGCTCT CCCCCCTGATGACTGCCTCTTACA CTGGCATAGCCT GATG (516) GGGC (517) 276 chr17: chr17:GGAGCAGTGCAG GGAGCAGTGCAG 0 27 4.81 1.14E−04 3′ss CLL 71198039-7119916271198039-71199138 TTGTGAAATCAT TTGTGAAAGTTT TACTTCTAGATG TGATTCATGGATATGC (31) TCAC (32) 277 chr6: chr6: AACCGGGGGAGC AACCGGGGGAGC 0 27 4.818.95E−03 3′ss CLL 41040823-41046743 41040823-41046767 GAGGCACGTTTCGAGGCACGGAGT TTTCCCCACCTT GTACCTCACAGC TCTA (518) CTTC (519) 278 chr11:chr11: CACACAGACTGC CACACAGACTGC 1 54 4.78 3.38E−06 3′ss CLL62376298-62376433 62376277-62376433 GTTCGATGAGTG GTTCGATGCCTTTCTTCCCCCTGC GCTGTTCACCCT CTTA (520) GATG (521) 279 chr14: chr14:AGTTAGAATCCA AGTTAGAATCCA 0 26 4.75 9.14E−07 3′ss CLL 74358911-7436047874358911-74360499 AACCAGAGTGTT AACCAGAGCTCC GTCTTTTCTCCC TGGTACAGTTTGCCCA (61) TTCA (62) 280 chr11: chr11: CATAAAATTCTA CATAAAATTCTA 2 794.74 1.89E−06 3′ss CLL 4104212-4104471 4104212-4104492 ACAGCTAATTCTACAGCTAAGCAA CTTTCCTCTGTC GCACTGAGCGAG TTCA (69) GTGA (70) 281 chr17:chr17: AGACCTACCAGA AGACCTACCAGA 0 25 4.70 1.18E−02 3′ss CLL62574712-62576906 62574694-62576906 AGGCTATGTGTT AGGCTATGAACATATTAATTTTAC GAGGACAACGCA AGAA (39) ACAA (40) 282 chr7: chr7:GTTTTTACCTCT GTTTTTACCTCT 1 49 4.64 1.80E−08 3′ss CLL 76943820-7695004176943806-76950041 GCCTCCTGATCT GCCTCCTGGTTT CTCATCCTAGGT TCATACTCTGCATTTC (522) CACC (523) 283 chr20: chr20: AGAACTGCACCT AGAACTGCACCT 0 244.64 3.30E−05 3′ss CLL 62701988-62703210 62701988-62703222 ACACACAGCCCTACACACAGGTGC GTTCACAGGTGC AGACCCGCAGCT AGAC (29) CTGA (30) 284 chr3:chr3: CACTGCTGGGAG CACTGCTGGGAG 0 24 4.64 1.42E−07 3′ss CLL129284872-129285369 129284860-129285369 AGTGGAAGTTGC AGTGGAAGATTCTTCCACAGATTC CTGAGAGCTGCC CTGA (524) GGCC (525) 285 chr11: chr11:GATTTTGGAGAG GATTTTGGAGAG 0 23 4.58 1.27E−04 3′ss CLL 33080641-3308306033080641-33083075 GCAACCAACTTT GCAACCAAATTC GTTTTTCACAGA CCTGGACTTTGTTTCC (526) CACC (527) 286 chr1: chr1: TCACTCAAACAG TCACTCAAACAG 0 234.58 1.48E−03 3′ss CLL 179835004-179846373 179834989-179846373TAAACGAGTTTT TAAACGAGGTAT ATCATTTACAGG GTGACGCATTCC TATG (53) CAGA (54)287 chr2: chr2: TGCAGAACTGGA TGCAGAACTGGA 0 23 4.58 2.35E−02 3′ss CLL23977668-23980287 23977644-23980287 TAAAGAAGTGTA TAAAGAAGGTGCTTTTTTTGTCTC TTCTAAAGTAAA AATT (528) GAAA (529) 288 chr5: chr5:ACTCTTATGCAG ACTCTTATGCAG 0 23 4.58 4.37E−03 3′ss CLL 1579622-15850981581810-1585098 TCCCCATGAGGT TCCCCATGAGGA TATGCTTATGTT GATCCTAGTCTC TCTC(530) ACCA (531) 289 chr6: chr6: AGTGTTTTACCA AGTGTTTTACCA 0 23 4.582.41E−04 3′ss CLL 30884736-30884871 30884736-30884881 TGGATGTTGTCATGGATGTTGGCT TTCCAGGGCTCC CCTCAGTGGCTG TCAG (532) TGAC (533) 290 chr6:chr6: TTTATGATGCTG TTTATGATGCTG 0 23 4.58 1.66E−02 3′ss CLL49416664-49419178 49416640-49419178 CTTTAAAGTTTT CTTTAAAGCTCAGTTAATGTTTTT TTAATGAAATTG CTTT (534) AAGA (535) 291 chr8: chr8:ATCTAAAAACAG ATCTAAAAACAG 0 23 4.58 3.15E−03 3′ss CLL 61741365-6174286861741365-61742880 AAGAGCAGGTCC AAGAGCAGGTGC TTTTTTAGGTGC AAAAACTTCAAGAAAA (536) CTAT (537) 292 chr2: chr2: AGCAAGTAGAAG AGCAAGTAGAAG 2 684.52 3.76E−08 3′ss CLL 109102364-109102954 109102364-109102966TCTATAAAATTT TCTATAAAATAC ACCCCCAGATAC AGCTGGCTGAAA AGCT (1) TAAC (2)293 chr15: chr15: GGATTGCAGCCA GGATTGCAGCCA 0 22 4.52 5.30E−05 3′ss CLL72859518-72862504 72859518-72862517 ACACAAAGTTTC ACACAAAGGAATTCTTCATAGGAA GTCCCAAATGCC TGTC (538) ATGT (539) 294 chr5: chr5:GGTTTCGAGTTT GGTTTCGAGTTT 0 22 4.52 1.57E−02 3′ss CLL109181707-109183328 109181707-109183357 GAATAGTGTTTT GAATAGTGGTCAGCTTGTTTGTTT GATTGAAGTTAT GTTT (540) CATG (541) 295 chr9: chr9:AAATGAAGAAAC AAATGAAGAAAC 0 22 4.52 5.36E−04 3′ss CLL125759640-125760854 125759640-125760875 TCCTAAAGCCTC TCCTAAAGATAATCTCTTTCTTTG AGTCCTGTTTAT TTTA (67) GACC (68) 296 chr11: chr11:GGATGACCGGGA GGATGACCGGGA 2 65 4.46 7.66E−06 3′ss CLL 71939542-7193969071939542-71939770 TGCCTCAGTCAC TGCCTCAGATGG TTTACAGCTGCA GGAGGATGAGAATCGT (47) GCCC (48) 297 chr11: chr11: CCACCGCCATCG CCACCGCCATCG 2 654.46 2.31E−08 3′ss CLL 64877395-64877934 64877395-64877953 ACGTGCAGTACCACGTGCAGGTGG TCTTTTTACCAC GGCTCCTGTACG CAGG (167) AAGA (168) 298 chr19:chr19: TGCCTGTGGACA TGCCTGTGGACA 0 21 4.46 1.50E−04 3′ss CLL14031735-14034130 14031735-14034145 TCACCAAGCCTC TCACCAAGGTGCGTCCTCCCCAGG CGCCTGCCCCTG TGCC (59) TCAA (60) 299 chr11: chr11:CGCAAGTACTTC CGCAAGTACTTC 0 20 4.39 2.24E−03 3′ss CLL 64676597-6467674264676622-64676742 CTGCCCCATCCA CTGCCCCAGGTA GCAGCACACAGT GTGGTGACTGTGGGGA (542) AACC (543) 300 chr22: chr22: TTCATAACAAAC TCATCAATGCCC 0 204.39 1.08E−04 5′ss CLL 24210086-24210667 24204389-24210667 CAGTAAATCACACGACCTTGCACA TTCAGGAATTCA TTCAGGAATTCA CCAA (544) CCAA (545) 301 chr2:chr2: AAATTTAACATT AAATTTAACATT 0 20 4.39 2.96E−02 3′ss CLL24207701-24222524 24207701-24222541 ACTCATAGTTTT ACTCATAGAGTATGCTGTTTTACA AGCCATATCAAA GAGT (546) GACT (547) 302 chr11: chr11:CACCGGGAGCTG CACCGGGAGCTG 2 59 4.32 8.17E−07 3′ss CLL 64119858-6412019864119858-64120215 CAGGGCCGCCCC CAGGGCCGGCAC TTGTCCATCCCA GAGCAGCTGCAGGGCA (548) GCCC (549) 303 chr11: chr11: GGAGGTGGACCT GGAGGTGGACCT 0 194.32 5.52E−04 3′ss CLL 68363686-68367788 68363686-68367808 GAGTGAACAATTGAGTGAACCACC TCTCCCCTCTTT CAACTGGTCAGC TTAG (189) TAAC (190) 304 chr11:chr11: ATTGGACACAGA CTGTCTCTAGGC 0 19 4.32 5.03E−04 5′ss CLL984190-984644 981299-984644 GATGGGATATCG TAAGCAGAATCG TGACGTCTGCATTGACGTCTGCAT CCAC (550) CCAC (551) 305 chr17: chr17: GGGACCTCACCAGGGACCTCACCA 0 19 4.32 5.14E−03 3′ss CLL 43522984-4352798343523029-43527983 AGCGCCCGCCCC AGCGCCCGATCT TCATCAACCTGC GCAGGCAGGCCCAGAT (552) TGAA (553) 306 chr9: chr9: CCAAGGACTGCA CCAAGGACTGCA 2 574.27 1.96E−04 3′ss CLL 139837449-139837800 139837395-139837800CTGTGAAGGCCC CTGTGAAGATCT CCGCCCCGCGAC GGAGCAACGACC CTGG (175) TGAC(176) 307 chr4: chr4: GAGTGTGAATCA GAGTGTGAATCA 2 56 4.25 3.01E−02 3′ssCLL 56874548-56875878 56874548-56875900 TCTGTGAATTTC TCTGTGAACCAGACATCACTCATT CTGAAAGAAACA TAAC (554) TTGG (555) 308 chr5: chr5:AGCATTGCTAGA AGCATTGCTAGA 1 37 4.25 3.83E−05 3′ss CLL139815842-139818078 139815842-139818045 AGCAGCAGCTTT AGCAGCAGGAATTGCAGATCCTGA TGGCAAATTGTC GGTA (19) AACT (20) 309 chr22: chr22:TCATCAATGCCC TCATCAATGCCC 0 18 4.25 3.60E−04 3′ss CLL 24204389-2420993824204389-24210667 CGACCTTGGTTC CGACCTTGCACA ATGAACACATTG TTCAGGAATTCAAGGT (556) CCAA (545) 310 chr3: chr3: GCATTTCTGAGA GCATTTCTGAGA 0 184.25 3.30E−03 3′ss CLL 38038678-38038959 38038678-38038973 AGGCTCGGGTCCAGGCTCGGGGGC TCTCCCGCAGGG TGGCTTTGACCT GCTG (557) ACAG (558) 311 chr6:chr6: GCCAGTCCAGAG GCCAGTCCAGAG 1 36 4.21 6.38E−07 3′ss CLL109767078-109767338 109767065-109767338 CCCTCAAGTTCT CCCTCAAGCTCTTCTTCTCAGCTC TGTGGCCATGGA TTGT (559) GAAG (560) 312 chr1: chr1:TGGCCGAGGCGC TGGCCGAGGCGC 2 54 4.20 1.35E−04 3′ss CLL 16803042-1680342416802999-16803424 TGACCAAGACCT TGACCAAGGCTG TACTCAGGGGAT AGGGCAGAGGAGCCTC (561) GCCT (562) 313 chr2: chr2: TCTACTTGGTGG TCTACTTGGTGG 3 724.19 1.68E−06 3′ss CLL 103348885-103353104 103348868-103353104GCTTCTTGCATT GCTTCTTGGATT TATTTTGTTTTA TGTTTGGTGTCA GGAT (563) GCAT(564) 314 chr14: chr14: GCTCCTGCTCAG GCTCCTGCTCAG 0 17 4.17 3.99E−043′ss CLL 78203438-78205120 78203418-78205120 TATATCCGTTTT TATATCCGATACTATCTGCTTTCT ACACCATCTCAG TCAG (565) CAAG (566) 315 chr3: chr3:GAAATAGGGCAC GAAATAGGGCAC 0 17 4.17 7.71E−03 3′ss CLL122152652-122156016 122152635-122156016 AGATCCAGTTTT AGATCCAGACTGTCTTTAATTTTA TGATAGATGCCA GACT (567) ACAT (568) 316 chr18: chr18:GCAACCTGTGTT GCAACCTGTGTT 1 33 4.09 3.11E−03 3′ss CLL 33724997-3372589633724997-33725910 TTACAAAGGTTT TTACAAAGATGG TATTTTTTAGAT TGTCCTACAGCAGGTG (569) GCCA (570) 317 chr7: chr7: GTATCAAAGTGT GTATCAAAGTGT 1 334.09 4.37E−04 3′ss CLL 94157562-94162500 94157562-94162516 GGACTGAGATTTGGACTGAGGATT GTCTTCCTTTAG CCATTGCAAAGC GATT (27) CACA (28) 318 chr4:chr4: CCCCTGAAGTAC CCCCTGAAGTAC 0 16 4.09 1.12E−04 3′ss CLL39868635-39871013 39868617-39871013 TAGCAAAGCATG TAGCAAAGGTACTTAATATTTTAT AGGCAATTAAAC AGGT (571) TTCT (572) 319 chr10: chr10:GTTCCTCACTTT GTTCCTCACTTT 1 31 4.00 1.17E−04 3′ss CLL 99502921-9950446899502921-99504485 GAATGAGGTGTT GAATGAGGGTGC TTTGATTCTGCA ATGGTACTCAGTGGTG (573) AGGT (574) 320 chr1: chr1: TCAGCCCTCTGA TCAGCCCTCTGA 0 154.00 6.99E−03 3′ss CLL 226036315-226036597 226036255-226036597ACTACAAAGGTG ACTACAAAACAG TTTGTTCACAGA AAGAGCCTGCAA GATC (93) GTGA (94)321 chr20: chr20: TCTTGGAAGGCA TCTTGGAAGGCA 0 15 4.00 4.25E−03 3′ss CLL31983014-31984566 31982922-31984566 GAGAAAAGATAT GAGAAAAGTCTATTCTAGAGCATT CCTCGAGACCTA TGGG (575) TGGC (576) 322 chr2: chr2:AACCCGGAGAGA AACCCGGAGAGA 0 15 4.00 5.64E−03 3′ss CLL 64456774-6445697864456774-64478252 AAAGGGAGTTTG AAAGGGAGCAAC TTTTTAGGTCAG TGATGTTGCCATAGTC (577) GCAG (578) 323 chr11: chr11: AATCTTCCCCAA AATCTTCCCCAA 1 303.95 7.37E−04 3′ss CLL 92887382-92895871 92887443-92895871 GATGTATGTTCTGATGTATGGTTA ATGTTCCAGCAG TATCAATCAGTG AGAT (579) AAAA (580) 324 chr18:chr18: CTCTCTTGTCAG CTCTCTTGTCAG 1 30 3.95 2.23E−02 3′ss CLL43459192-43460039 43459179-43460039 ACAAGCAGTTGT ACAAGCAGGTAACTCTTCCAGGTA TGGAGACTATAC ATGG (581) AGTG (582) 325 chr5: chr5:GCAGAGCTGTGG GCAGAGCTGTGG 1 30 3.95 1.23E−03 3′ss CLL138724290-138725368 138724274-138725368 CTTACCAGTCCC CTTACCAGATGTTCCTTGTTCCAG GGCAAAATCTGG ATGT (583) CAAA (584) 326 chr17: chr17:TGCAGGAGACCG TGCAGGAGACCG 1 29 3.91 7.83E−03 3′ss CLL 58163509-5816555758163487-58165557 GCTTTTGGGTCC GCTTTTGGATAC CCTTCTTATACC TGCTAATCAGTCCCTC (585) CTAG (586) 327 chr1: chr1: AGTTACAACGAA AGTTACAACGAA 1 293.91 2.95E−05 3′ss CLL 185056772-185060696 185056772-185060710CACCTCAGTGAC CACCTCAGGAGG TCTTTTACAGGA CAATAACAGATG GGCA (162) GCTT(163) 328 chr10: chr10: TCTTGCCAGAGC TCTTGCCAGAGC 0 14 3.91 5.04E−053′ss CLL 99219232-99219415 99219283-99219415 TGCCCACGCTCT TGCCCACGCTTCCCACCCTCAGCT TTTCCTTGCTGC GCCT (587) TGGA (588) 329 chr4: chr4:CCATGGTCAAAA CCATGGTCAAAA 0 14 3.91 4.36E−02 3′ss CLL152022314-152024139 152022314-152024022 AATGGCAGCACC AATGGCAGACAAAACAGGTCCGCC TGATTGAAGCTC AAAT (344) ACGT (345) 330 chr1: chr1:ATCAGAAATTCG ATCAGAAATTCG 3 57 3.86 4.89E−06 3′ss CLL212515622-212519131 212515622-212519144 TACAACAGGTTT TACAACAGCTCCCTTTTAAAGCTC TGGAGCTTTTTG CTGG (65) ATAG (66) 331 chr1: chr1:GCAGGCTGCCCG GCAGGCTGCCCG 4 69 3.81 2.04E−07 3′ss CLL156552962-156553113 156552962-156553129 GGACTCTGGCTC GGACTCTGGGGATCTTTCTCTCAG CATGAAGGGACA GGGA (589) GTGG (590) 332 chr6: chr6:GCCAGTCCAGAG GCCAGTCCAGAG 2 41 3.81 4.40E−03 3′ss CLL109767165-109767338 109767065-109767338 CCCTCAAGTCTT CCCTCAAGCTCTTACCAGACTTGC TGTGGCCATGGA AGGG (591) GAAG (560) 333 chr20: chr20:ACATGAAGGTGG ACATGAAGGTGG 5 81 3.77 1.48E−08 3′ss CLL 34144042-3414472534144042-34144743 ACGGAGAGGCTC ACGGAGAGGTAC CCCTCCCACCCC TGAGGACAAATCAGGT (49) AGTT (50) 334 chr17: chr17: CTATTTCACTCT CTATTTCACTCT 1 253.70 2.79E−05 3′ss CLL 7131030-7131295 7131102-7131295 CCCCCGAACCTACCCCCGAAATGA TCCAGGTTCCTC GCCCATCCAGCC CTCC (33) AATT (34) 335 chr6:chr6: TTCCCACTGGTC TTCCCACTGGTC 1 25 3.70 3.91E−03 3′ss CLL110085185-110086201 110085185-110086215 GCCTGCAGGTAT GCCTGCAGACTGTTCTCTTTAGAC GCATCCTTCGAA TGGC (592) CCAA (593) 336 chr7: chr7:TGTAAATGGGGA TGTAAATGGGGA 1 25 3.70 2.18E−05 3′ss CLL 889240-889468889240-889559 AGCGCTGTTTTC AGCGCTGTGCGA TACAGACTGCCA CGACTGTAAGGG TTGC(594) CAAG (595) 337 chr12: chr12: TCAATGCAAATA TCAATGCAAATA 0 12 3.701.92E−03 3′ss CLL 112915534-112915638 112915534-112915660 TCATCATGGATTTCATCATGCCTG TTCTTCCTAAAT AATTTGAAACCA TTCT (596) AGTG (597) 338 chr14:chr14: ACAAATCAACTG ACAAATCAACTG 0 12 3.70 1.38E−03 3′ss CLL56100059-56101230 56100059-56101243 GAAAGCAATTAC GAAAGCAAGCAGTGTTTTCAGGCA TCTGCAGAACTA GTCT (598) AATA (599) 339 chr17: chr17:CAAAGCGCCCAG CAAAGCGCCCAG 0 12 3.70 2.10E−02 3′ss CLL 2266428-22667272266428-2266758 CCCTGGGGGCTG CCCTGGGGATCC GAGGCTGAGCCC GGAAACGGCACT CGGC(600) CAAG (601) 340 chr19: chr19: TGACACAGCCCT TGACACAGCCCT 0 12 3.704.53E−05 3′ss CLL 16264018-16265158 16264018-16265208 GCAGGCAGGACCGCAGGCAGAAGG TTTCCCCCTCCC ATCCCGCAAACG TAGT (602) TGGA (511) 341 chr1:chr1: AGTTGCCATTCC AGTTGCCATTCC 0 12 3.70 4.52E−03 3′ss CLL186324917-186325417 186324900-186325417 ATTACATGTCTT ATTACATGCTTCTACTTTCCTGAA AAGCTTAGATGA GCTT (603) TGTT (604) 342 chr3: chr3:ACTGATTAAAAA ACTGATTAAAAA 4 62 3.66 9.33E−05 3′ss CLL 56649300-5664993156649300-56649949 TCTTGGTGGTGA TCTTGGTGTTGA TTTCTCTTTGCC TACAATACAAATAGTT (605) GGAA (606) 343 chr6: chr6: CCGGGGCCTTCG CCGGGGCCTTCG 4 583.56 3.53E−06 3′ss CLL 10723474-10724788 10723474-10724802 TGAGACCGCTTGTGAGACCGGTGC TTTTCTGCAGGT AGGCCTGGGGTA GCAG (95) GTCT (96) 344 chr3:chr3: AGGCTATTGTTG AGGCTATTGTTG 1 22 3.52 2.36E−03 3′ss CLL184587316-184588487 184587316-184588503 CAGACCGGGCTG CAGACCGGATGGTTTTCCTTACAG TAGAAATCCTAT ATGG (607) TCCA (608) 345 chr4: chr4:CCTTTCAAGAAA CCTTTCAAGAAA 1 22 3.52 1.60E−02 3′ss CLL 3124663-31259763124663-3127275 ACAAAAAGTCGC ACAAAAAGGCAA TTTTTCCAGTGG AGTGCTCTTAGG CGGT(609) AGAA (610) 346 chr9: chr9: ACACGGAGCTCA ACACGGAGCTCA 2 33 3.501.45E−05 3′ss CLL 123933826-123935634 123933826-123935520 AGAAACAGTTTCAGAAACAGATGG TTCCAGAACTAC CAAACCAAAAAG CAGC (611) ATTT (612) 347 chr19:chr19: CAAGCAGGTCCA CAAGCAGGTCCA 6 76 3.46 9.28E−05 3′ss CLL5595521-5598803 5595508-5598803 AAGAGAGATTTT AAGAGAGAAGCT GGTAAACAGAGCCCAAGAGTCAGG TCCA (138) ATCG (139) 348 chr5: chr5: GACTTCGAACATGACTTCGAACAT 4 54 3.46 7.66E−03 3′ss CLL 78608321-7861019278608321-78610079 TTAAACAGTGTG TTAAACAGAGGT TTACAGGTAGAA ATCCTGGGCAAGGAGA (613) TCAT (614) 349 chr2: chr2: ACCACGAAGGGT ACCACGAAGGGT 2 323.46 1.25E−02 3′ss CLL 231050873-231065600 231050859-231065600CACACAAGTCTA CACACAAGGGGC TTTGGTCCAGGG AGCCTCACCTGG GCAG (615) GCAT(616) 350 chr1: chr1: CGATCTCCCAAA CGATCTCCCAAA 1 21 3.46 1.57E−05 3′ssCLL 52880319-52880412 52880319-52880433 AGGAGAAGTCTG AGGAGAAGCCCCACCAGTCTTTTC TCCCCTCGCCGA TACA (55) GAAA (56) 351 chr2: chr2:TTAACAAACACG TGCTGGCACACC 0 10 3.46 8.22E−03 5′ss CLL 69015785-6903440469015088-69034404 TGAATCTACAGT CTGTGGAGCAGT GTTTGGCCAGCG GTTTGGCCAGCGCTTG (617) CTTG (618) 352 chr5: chr5: CGCCCCAGGGCA CGCCCCAGGGCA 0 103.46 1.97E−03 3′ss CLL 156915521-156916109 156915497-156916109AGCGAAAGGTGT AGCGAAAGGTGA TCCTTGACTTGT TCAACACTCCGG GCGT (619) AAAT(620) 353 chr9: chr9: TGGTACAACTTC TGGTACAACTTC 0 10 3.46 6.70E−03 3′ssCLL 115934002-115935732 115933986-115935732 AGGAAAAGTCTG AGGAAAAGTGTTTTTGTTTTGCAG TAGCCCTCCAGG TGTT (621) CCCA (622) 354 chr14: chr14:TGGATTTGCTCG TGGATTTGCTCG 1 20 3.39 1.52E−04 3′ss CLL 50808004-5080884950807950-50808849 GCTTTTGATTTT GCTTTTGACTGG GATTCCAGCCTT ACCGAGTGACTACCGC (623) CTAT (624) 355 chr18: chr18: GATGAGGACCCC GATGAGGACCCC 5 613.37 3.06E−06 3′ss CLL 9133520-9136361 9133508-9136361 CACATAGGTTTCCACATAGGGATG CAAACCAGGATG GCCATAGCAGCC GCCA (625) ACAA (626) 356 chr10:chr10: TACCTCTGGTTC TACCTCTGGTTC 3 39 3.32 2.21E−05 3′ss CLL99214556-99215395 99214556-99215416 CTGTGCAGTCTT CTGTGCAGTTCTCGCCCCTCTTTT GTGGCACTTGCC CTTA (13) CTGG (14) 357 chr2: chr2:TGTTTTAAATTC TGTTTTAAATTC 2 29 3.32 8.44E−06 3′ss CLL225670231-225670842 225670246-225670842 CATAGCAGCTAT CATAGCAGCATTTTCTACAGTAAA TTCATCAATAGC CCAT (627) TATT (628) 358 chrX: chrX:GCTGGGATGTTA GCTGGGATGTTA 1 19 3.32 2.06E−02 3′ss CLL153323986-153357641 153298008-153357641 GGGCTCAGCCTG GGGCTCAGGGAATCGTTCCAGGAC GAAAAGTCAGAA CCAG (629) GACC (630) 359 chr16: chr16:CTGGTTATTGCA CTGGTTATTGCA 0 9 3.32 6.10E−05 3′ss CLL 72139523-7213988272139523-72139903 AATTAAAGCTCT AATTAAAGGTCT TTGCCGTCCCCT TCAACCCCAGGACCTA (631) TTGG (632) 360 chr5: chr5: CTCCATGCTCAG CTCCATGCTCAG 4 483.29 1.01E−06 exon CLL 869519-870587 865696-870587 CTCTCTGGTTTCCTCTCTGGGGAA incl. TTTCAGGGCCTG GGTGAAGAAGGA CCAT (128) GCTG (129) 361chrX: chrX: GGTCATGCTAAT GGTCATGCTAAT 8 82 3.21 5.22E−07 3′ss CLL70516897-70517210 70516897-70517226 GAGACAGGTCTG GAGACAGGATTTTTGTTTTTTTAG GATGAGGCGCCA ATTT (633) AGAA (634) 362 chr16: chr16:GTCAGCATTTGC GTCAGCATTTGC 2 26 3.17 7.43E−04 3′ss CLL 47347747-4739969847347734-47399698 AGACTTTGTTTC AGACTTTGATGG TTTTGGCAGATG AGATGGACACATGAGA (635) GGAT (636) 363 chr5: chr5: GCAGAGCTGTGG GCAGAGCTGTGG 2 263.17 1.17E−03 3′ss CLL 138725125-138725368 138724274-138725368CTTACCAGACTT CTTACCAGATGT CTCCCTTTCCAG GGCAAAATCTGG GCCC (637) CAAA(584) 364 chr11: chr11: CGGCGCGGGCAA CGGCGCGGGCAA 0 8 3.17 6.70E−03 3′ssCLL 62648919-62649352 62648919-62649364 CCTGGCGGCCCC CCTGGCGGGTCTCATTTCAGGTCT GAAGGGGCGTCT GAAG (165) CGAT (166) 365 chr11: chr11:TGCAGCTGGCCC TGCAGCTGGCCC 0 8 3.17 2.22E−02 3′ss CLL 64002365-6400291164002365-64002929 CCGCCCAGGTCT CCGCCCAGGCCC TTTCTCTCCCAC CTGTCTCCCAGCAGGC (638) CTGA (639) 366 chr14: chr14: CACAGCAAGCAC CACAGCAAGCAC 0 83.17 3.01E−05 3′ss CLL 31169464-31171484 31169464-31171501 CTTCTGAGTTCTCTTCTGAGGCTG TTTCTTATTTCA ATTTGGAGCAAT GGCT (640) ATAA (641) 367 chr1:chr1: TCACACCTGTAG TCACACCTGTAG 0 8 3.17 9.33E−05 3′ss CLL186300728-186301326 186300713-186301326 GAACTGAGTGTA GAACTGAGGAAGTTATGATACAGG AAGTTATGGCAG AAGA (642) AAGA (643) 368 chr5: chr5:AAAATTGACTAT AAAATTGACTAT 0 8 3.17 7.30E−03 3′ss CLL 169101449-169108733169101449-169108747 GGCAACAATTTT GGCAACAAAATC TGCTTTACAGAA CTTGAGCTTGATTCCT (644) TTGA (645) 369 chr9: chr9: ACACGGAGCTCA ACACGGAGCTCA 0 8 3.175.42E−04 3′ss CLL 123933826-123935644 123933826-123935520 AGAAACAGAACTAGAAACAGATGG ACCAGCAGATCT CAAACCAAAAAG AGAA (646) ATTT (612) 370 chr10:chr10: GGGAGGAAAAGT GGGAGGAAAAGT 5 52 3.14 1.27E−03 3′ss CLL112058568-112060304 112058548-112060304 AATTAATGTTTT AATTAATGGAAGTGTTTTTCTTTT TTATAGAACTAA TTAG (647) CCAA (648) 371 chr3: chr3:ATTTGGATCCTG ATTTGGATCCTG 4 43 3.14 1.46E−04 3′ss CLL196792335-196792578 196792319-196792578 TGTTCCTCTTTT TGTTCCTCATACTTTCTGTTAAAG AACTAGACCAAA ATAC (87) ACGA (88) 372 chr12: chr12:ATTTGGACTCGC ATTTGGACTCGC 3 34 3.13 1.20E−04 3′ss CLL105601825-105601935 105601807-105601935 TAGCAATGATGT TAGCAATGAGCACTGTTTATTTTT TGACCTCTCAAT AGAG (41) GGCA (42) 373 chr19: chr19:CTATGGGCTCAC CTATGGGCTCAC 7 67 3.09 2.90E−04 3′ss CLL 41084118-4108435341084118-41084367 TCCTCTGGTCCT TCCTCTGGTTCG CCTGTTGCAGTT TCGCCTGCAGCTCGTC (169) TCGA (170) 374 chr11: chr11: TTCTCCAGGACC TTCTCCAGGACC 1 163.09 4.69E−03 3′ss CLL 125442465-125445146 125442465-125445158TTGCCAGACCTT TTGCCAGAGGAA TTCTATAGGGAA TCAAAGACTCCA TCAA (150) TCTG(151) 375 chr12: chr12: AGAAGGAGCTGC AGAAGGAGCTGC 1 16 3.09 2.88E−033′ss CLL 110437589-110449795 110437589-110449809 AGGGCCAGTGTTAGGGCCAGAATG TCCTTCACAGAA TGGAGGCTGTGG TGTG (649) ACCC (650) 376 chr8:chr8: GCTCTGGAGAAT GCTCTGGAGAAT 4 41 3.07 6.90E−07 3′ss CLL126051218-126052036 126051201-126052036 CTCAATAAGGTT CTCAATAAGGCTTTTCTTCCTTTA CTCCTAGCAGAC GGGC (651) ATTG (652) 377 chr3: chr3:CATGCAATGAAC CATGCAATGAAC 2 24 3.06 7.00E−06 3′ss CLL 42674315-4267510942674315-42675071 CCAAAAGGTTGA CCAAAAGGTCAC TTCCAGTGCTAA TCTGAGAGGAGTAAGG (653) GATA (654) 378 chr5: chr5: TGCTTCCGGAAC TGCTTCCGGAAC 6 573.05 3.26E−05 3′ss CLL 139941307-139941428 139941286-139941428AGTGACAGCCCC AGTGACAGGGAC ATCTCTGCCCCT TTCGCTTTTGTG GCTA (655) GCAA(656) 379 chr12: chr12: TGGGTTTCAGCA TGGGTTTCAGCA 0 7 3.00 4.31E−03 3′ssCLL 64199184-64202434 64199184-64202454 AGAGAACATTGT AGAGAACACTGGTTTTCTGATTTT CAGCCTCAGGAA CTAG (657) ACAA (658) 380 chr18: chr18:AGGACATGGATT AGGACATGGATT 0 7 3.00 4.13E−03 3′ss CLL 47311742-4731366047311721-47313660 TGGTAGAGTGCT TGGTAGAGGTGA CTAATTTTTGTT ATGAAGCTTTTGTTAA (659) CTCC (660) 381 chr19: chr19: ATCACAACCGGA ATCACAACCGGA 0 73.00 2.46E−02 3′ss CLL 15491444-15507960 15491423-15507960 ACCGCAGGCTCCACCGCAGGCTCA TTCTGCCCTGCC TGATGGAGCAGT CGCA (661) CCAA (662) 382 chr1:chr1: CAGGAAGCAGCT CAGGAAGCAGCT 0 7 3.00 7.09E−04 3′ss CLL46068037-46070588 46068037-46070607 AGTCTTTTATGT AGTCTTTTAGGTTTATTCTCTTTG AAGAAGTATGGA TAGA (663) GAGA (664) 383 chr21: chr21:GAACCAATGGAA GAACCAATGGAA 0 7 3.00 1.40E−02 3′ss CLL 45452053-4545268245452053-45457672 TGGAGAAGGCAC TGGAGAAGGTCC AGGCGTTTTGCA TATGGCCGGGCTAAGG (665) CCGA (666) 384 chr2: chr2: TGCTTGTAAAAT TGCTTGTAAAAT 0 7 3.001.13E−02 3′ss CLL 160673561-160676236 160673543-160676236 TGAAATGGTGCTTGAAATGGTTGA TTTAATTATTAT CTACAAAGAAGA AGTT (667) ATAT (668) 385 chr5:chr5: ACTCGCGCCTCT ACTCGCGCCTCT 0 7 3.00 4.59E−02 3′ss CLL150411955-150413168 150411944-150413168 TCCATCTGTTTT TCCATCTGCCGGGTCGCAGCCGGA AATACACCTGGC ATAC (109) GTCT (110) 386 chr7: chr7:CCACCTCACCAT CCACCTCACCAT 0 7 3.00 2.08E−02 3′ss CLL 99954506-9995585399954506-99955842 CACCCAGGCCCC CACCCAGGCCCT TCCACAGGGCCC CAGGCAGCCCCTCTCT (669) CCAC (515) 387 chr4: chr4: CGTCTCCATGAC CGTCTCCATGAC 6 542.97 7.33E−05 3′ss CLL 995351-995438 995351-995466 CATGCAAGGTGTCATGCAAGGCTT AGACGCAGTGCT CCTGAACTACTA CCCC (670) CGAT (671) 388 chr15:chr15: AGGAGGCAATTA AGGAGGCAATTA 8 68 2.94 1.81E−04 3′ss CLL75131104-75131350 75131086-75131350 AGGCAAAGGCCC AGGCAAAGGTGGTTTCCCTGCTAC GGCAGTACGTGT AGGT (672) CCCG (673) 389 chrX: chrX:TACAAGAGCTGG TACAAGAGCTGG 2 22 2.94 1.26E−04 3′ss CLL153699660-153699819 153699660-153699830 GTGGAGAGGGTC GTGGAGAGGTATCCAACAGGTATT TATCGAGACATT ATCG (158) GCAA (159) 390 chr9: chr9:CACCACGCCGAG CACCACGCCGAG 5 43 2.87 3.76E−08 3′ss CLL125023777-125026993 125023787-125026993 GCCACGAGACAT GCCACGAGTATTTGATGGAAGCAG TCATAGACATTG AAAC (142) ATGG (143) 391 chr14: chr14:TTACCTCCGAAG TTACCTCCGAAG 10 79 2.86 3.40E−05 3′ss CLL 23242937-2324314123242925-23243141 GATCGTGGTTCT GATCGTGGGGTC CTTTGTAGGGTC TGCCACAAGGTATGCC (674) CCTC (675) 392 chr11: chr11: AATAAGCCCTCA AATAAGCCCTCA 0 62.81 1.66E−02 3′ss CLL 67376193-67376896 67376193-67376922 GATGGCAGCCTGGATGGCAGGCCC TCTGACCTGTGG AAGTATCTGGTG GCCC (676) GTGA (677) 393 chr16:chr16: ACTCCCAGCTCA ACTCCCAGCTCA 0 6 2.81 1.49E−02 3′ss CLL56403209-56419830 56403239-56419830 ATGCAATGGTTC ATGCAATGGCTCCATACCATCTGG ATCAGATTCAAG TACT (332) AGAT (333) 394 chr17: chr17:GCCTGGACCTGT GCCTGGACCTGT 0 6 2.81 4.26E−02 3′ss CLL 43316432-4331787543316432-43317842 ACTTGGAGGTGC ACTTGGAGAGGC AGATCCAGGCGT TTCGGCTCACCGACCT (678) AGAG (679) 395 chr21: chr21: CTGTAACTACTA CTGTAACTACTA 0 62.81 3.47E−04 3′ss CLL 47655360-47656742 47655340-47656742 GCCCACAGTTTCGCCCACAGAGTG TTTTTTATTCAA ACATGATGAGGG ATAG (680) AGCA (681) 396 chr3:chr3: CTCTCAATGCAG CTCTCAATGCAG 0 6 2.81 1.49E−03 3′ss CLL71019345-71019886 71015207-71019886 CTTTACAGTTTT CTTTACAGGCTTCCTGCAGATTGT CAATGGCTGAGA TCAA (682) ATAG (683) 397 chr9: chr9:GGAGCAGTTCCA GGAGCAGTTCCA 0 6 2.81 4.44E−03 3′ss CLL 95007367-9500965895007353-95009658 GAAGACTGCTGC GAAGACTGGGAC TTCTCCATAGGG CATTGTTGTGGAACCA (684) AGGC (685) 398 chrX: chrX: CCTGCTGGACCA CCTGCTGGACCA 0 6 2.811.25E−02 3′ss CLL 48340103-48340769 48340103-48340796 TTCTTACGTTGTTTCTTACGATTT CTCCCCCTGTTC CAACCAGCTGGA CTAA (686) TGGT (687) 399 chr20:chr20: GGATTTTGATAA GGATTTTGATAA 7 53 2.75 1.01E−03 3′ss CLL36631195-36634598 36631178-36634598 TGAAGAAGTTGT TGAAGAAGAGGAGCTCTTTTTCCA ACAGTCAGTCCC GAGG (688) TCCC (689) 400 chr4: chr4:CGTCTCCATGAC CGTCTCCATGAC 3 26 2.75 5.89E−04 3′ss CLL 995351-995433995351-995466 CATGCAAGGGCA CATGCAAGGCTT GGTGTAGACGCA CCTGAACTACTA GTGC(690) CGAT (671) 401 chr15: chr15: TGATTCCAAGCA TGATTCCAAGCA 2 19 2.743.63E−05 3′ss CLL 25213229-25219533 25213229-25219457 AAAACCAGCCTTAAAACCAGGCTC CCCCTAGGTCTT CATCTACTCTTT CAGA (230) GAAG (231) 402 chr18:chr18: AGTGCCAGCTGC AGTGCCAGCTGC 2 19 2.74 1.04E−03 exon CLL47811617-47812118 47811721-47812118 GGGCCCGGCTCT GGGCCCGGGAAT skipCACCAGTGACGC CGTACAAGTACT CCTC (691) TCCC (692) 403 chr18: chr18:AACTTACTTTGT AACTTACTTTGT 2 19 2.74 1.46E−04 3′ss CLL 66356291-6635853166355002-66358531 TTATGATGCTTT TTATGATGAGTA TATTTTAGATTC TGAAGATGGTGAAGAG (693) TCTG (694) 404 chr21: chr21: ATCATAGCCCAC ATCATAGCCCAC 3 252.70 2.17E−02 3′ss CLL 37416267-37417879 37416254-37417879 ATGTCCAGTTTTATGTCCAGGTAA TCTTTCTAGGTA AAGCAGCGTTTA AAAG (695) ATGA (696) 405 chrX:chrX: TGACTCCGCTGC TGACTCCGCTGC 1 12 2.70 2.07E−02 3′ss CLL118923962-118925536 118923974-118925536 TCGCCATGACTT TCGCCATGTCTTTCAGGATTAAGC CTCACAAGACTT GATT (697) TCAG (698) 406 chr1: chr1:CCAAGCACCTGA CCAAGCACCTGA 7 50 2.67 1.87E−03 3′ss CLL100606070-100606400 100606070-100606522 AACAGCAGTTTG AACAGCAGATGCCAGGCTTCTATT TGAAAAAGTTCA TTAG (699) CTTC (700) 407 chr12: chr12:GCCTGCCTTTGA GCCTGCCTTTGA 13 88 2.67 1.74E−07 3′ss CLL113346629-113348840 113346629-113348855 TGCCCTGGATTT TGCCCTGGGTCATGCCCGAACAGG GTTGACTGGCGG TCAG (71) CTAT (72) 408 chr7: chr7:CGAGCTGTTGGC CGAGCTGTTGGC 7 49 2.64 2.27E−05 3′ss CLL149547427-149549949 149547427-149556510 ATCCTTGGTTTC ATCCTTGGGACCTTGTCCACAGGA TGCCGCTGCCAA GAAG (701) GCCA (702) 409 chr11: chr11:GCTTTCTACGGA GCTTTCTACGGA 3 24 2.64 1.08E−04 3′ss CLL126142974-126143210 126142974-126143230 ACATCAATGAGC ACATCAATGAGTTTCTGTCTGCAC ACCTGGCCGTAG ACAG (703) TCGA (704) 410 chr8: chr8:TTATTTTACACA TTATTTTACACA 3 24 2.64 2.89E−05 3′ss CLL 38095145-3809562438095145-38095606 ATCCAAAGCCAG ATCCAAAGCTTA TTGCAGGGTCTG TGGTGCATTACCATGA (57) AGCC (58) 411 chr12: chr12: CAGGAATACCTG CAGGAATACCTG 1 112.58 2.06E−06 3′ss CLL 62783294-62783413 62783294-62783384 CAGATAAGATTTCAGATAAGATGA CACAGAATATTC TAGTTACTGATA GCTA (705) TATA (706) 412 chr17:chr17: CTACACCAAGAA CTACACCAAGAA 1 11 2.58 2.56E−03 3′ss CLL18007203-18007857 18007203-18007936 GAGAGGACCTCT GAGAGGACAGAGTCCCTCGCGCAG GCCAGACTTCAC AATC (707) AGAC (708) 413 chr17: chr17:CGGAGGCTGTCT CGGAGGCTGTCT 1 11 2.58 4.39E−03 3′ss CLL 73486839-7348711073486839-73487129 CCTCTCAGACTT CCTCTCAGGAAA CCTCTCTCCCAC TGCTGCGCTGCACAGG (709) TTTG (710) 414 chr11: chr11: TCCTGCTGGAGC TCCTGCTGGAGC 0 52.58 5.77E−03 3′ss CLL 68331900-68334466 68331900-68334481 CACCCAAGCTTTCACCCAAGAAAA TTCTTCTTCAGA GTGTGATGAAGA AAAG (711) CCAC (712) 415 chr13:chr13: AGCTGAAATTTC AGCTGAAATTTC 0 5 2.58 3.85E−02 3′ss CLL113915073-113917776 113915073-113917800 CAGTAAAGGGGG CAGTAAAGCCTGGTTTTATTCTTC GAGATTTGAAAA TTTT (152) AGAG (153) 416 chr13: chr13:ACCAAGCATACT ACCAAGCATACT 0 5 2.58 1.04E−02 3′ss CLL 20656270-2065690520656270-20656920 TCCAGATGTTCT TCCAGATGGGTC CTCTATTTAAGG AATATTCTCTCGGTCA (713) AGTT (714) 417 chr19: chr19: CGGGCCGCCCCC CGGGCCGCCCCC 0 52.58 1.76E−03 3′ss CLL 36231397-36231924 36230989-36231924 CTGCCCGGTGTTCTGCCCGGAGGC CTTCTGGGCAGT CGGTCCCTGCCA GCAA (715) AGGG (716) 418 chr20:chr20: ACATGAAGGTGG ACATGAAGGTGG 0 5 2.58 3.36E−03 3′ss CLL34144042-34144761 34144042-34144743 ACGGAGAGTTCT ACGGAGAGGTACCTGTGACCAGAC TGAGGACAAATC ATGA (250) AGTT (50) 419 chr21: chr21:AAGATGTCCCTG AAGATGTCCCTG 0 5 2.58 3.03E−02 3′ss CLL 38570326-3857251438570326-38572532 TGAGGATTGTGT TGAGGATTGCAC GTTTGTTTCCAC TGGGTGCAAGTTAGGC (224) CCTG (225) 420 chr6: chr6: GGAGGACTGGGG GGAGGACTGGGG 0 5 2.582.97E−03 3′ss CLL 32095539-32095893 32095527-32095893 TCTGCAGACATTTCTGCAGAACAG TCTTGCAGACAG CACCTTGTATTC CACC (717) TGGC (718) 421 chr7:chr7: CTGCCCCCTGCG CTGCCCCCTGCG 0 5 2.58 7.48E−03 3′ss CLL44795898-44796008 44795898-44796023 CCACACGGCCTC CCACACGGTGATTTTCCCTGCAGT GGTTCATTCGCA GATG (719) TATG (720) 422 chr7: chr7:TGTAAATGGGGA TGTAAATGGGGA 0 5 2.58 2.68E−02 3′ss CLL 889240-889477889240-889559 AGCGCTGTACTG AGCGCTGTGCGA CCATTGCTATGC CGACTGTAAGGG ACGG(721) CAAG (595) 423 chr12: chr12: GGCCAGCCCCCT GGCCAGCCCCCT 10 62 2.521.37E−08 3′ss CLL 120934019-120934204 120934019-120934218 TCTCCACGGCCTTCTCCACGGTAA TGCCCACTAGGT CCATGTGCGACC AACC (206) GAAA (207) 424 chr9:chr9: CTGATGAAAACT CTGATGAAAACT 11 66 2.48 1.51E−04 3′ss CLL93641235-93648124 93641235-93650030 ACTACAAGCAGA ACTACAAGGCCCCACCTTACAGGC AGACCCATGGAA CAGG (722) AGTG (723) 425 chr17: chr17:TTCAGCTGCCCC TTCAGCTGCCCC 8 49 2.47 1.42E−05 3′ss CLL 57079102-5708968857079075-57089688 TGAAGAAGAAAC TGAAGAAGGAAT ATGTTCTCCTTC GAGTAGCGACAGCTTC (724) TGAC (725) 426 chr15: chr15: GAAACCAACTAA GAAACCAACTAA 3 212.46 9.18E−03 3′ss CLL 59209219-59224554 59209198-59224554 AGGCAAAGCCCAAGGCAAAGGTAA TTTTCCTTCTTT AAAACATGAAGC CGCA (101) AGAT (102) 427 chr7:chr7: TCCCGAAGCCAC TCCCGAAGCCAC 3 21 2.46 4.67E−04 3′ss CLL99752804-99752884 99752787-99752884 CTCATGAGCCTC CTCATGAGGTCGTGCCTTCCCCCA GGCAGTGTGATG GGTC (726) GAGC (727) 428 chr8: chr8:CCCCGGTGCGTA CCCCGGTGCGTA 1 10 2.46 2.22E−02 3′ss CLL145624052-145624168 145624028-145624168 AGGAGGAGCCTG AGGAGGAGGAGGCCCCCCTTTGGC ACAATCCCAAGG CCTG (728) GGGA (729) 429 chr9: chr9:AGCTGGAGAAAA AGCTGGAGAAAA 1 10 2.46 3.34E−04 3′ss CLL123932094-123935634 123932094-123935520 ACCTTCTTTTTC ACCTTCTTATGGTTCCAGAACTAC CAAACCAAAAAG CAGC (730) ATTT (731) 430 chr15: chr15:TTCGTTGGCAGC TTCGTTGGCAGC 6 37 2.44 2.59E−04 3′ss CLL 77327904-7732815177327904-77328142 TTCTGCTGAGAC TTCTGCTGCGTC CCTGACCCCCAC CACAGAGACCCTCCCC (732) GACC (733) 431 chr19: chr19: GTGCTTGGAGCC GTGCTTGGAGCC 5 312.42 4.69E−03 3′ss CLL 55776746-55777253 55776757-55777253 CTGTGCAGACTTCTGTGCAGCCTG TCCGCAGGGTGT GTGACAGACTTT GCGC (179) CCGC (180) 432 chr4:chr4: GTGCCAACGAGG GTGCCAACGAGG 10 57 2.40 1.64E−03 3′ss CLL184577127-184580081 184577114-184580081 ACCAGGAGTTCT ACCAGGAGATGGTTATTTCAGATG AACTAGAAGCAT GAAC (734) TACG (735) 433 chr16: chr16:CCTCACGATGCA CCTCACGATGCA 7 40 2.36 8.53E−04 3′ss CLL 67692735-6769283067692719-67692830 AGGCCACGAGTT AGGCCACGGGAG CATGTCCCACAG AAGCTGTGTACAGGAG (736) CTGT (737) 434 chr6: chr6: AGGGGGCTCTTT AGGGGGCTCTTT 14 752.34 3.51E−06 3′ss CLL 91269953-91271340 91269933-91271340 ATATAATGTTTGATATAATGTGCT TGCCTTTCTTTC GCATGGTGCTGA GCAG (265) ACCA (266) 435 chr15:chr15: TCACACAGGATA GCCTCACTGAGC 2 14 2.32 4.92E−03 exon CLL25212299-25213078 25207356-25213078 ATTTGAAAGTGT AACCAAGAGTGT incl.CAGTTGTACCCG CAGTTGTACCCG AGGC (164) AGGC (145) 436 chr9: chr9:AAAAATAAAGCC CTGATGAAAACT 1 9 2.32 3.99E−03 5′ss CLL 93648256-9365003093641235-93650030 TTTCCCAGGCCC ACTACAAGGCCC AGACCCATGGAA AGACCCATGGAAAGTG (738) AGTG (723) 437 chr14: chr14: CGAGGATGAAGA CGAGGATGAAGA 0 42.32 4.50E−03 3′ss CLL 34998676-35002649 34998681-35002649 CAGAGCAGGTGACAGAGCAGTACA CCAAGAAAAAAA GGTGACCAAGAA AGAA (739) AAAA (740) 438 chr2:chr2: AGACAAGGGATT AGACAAGGGATT 0 4 2.32 1.21E−02 3′ss CLL26437445-26437921 26437430-26437921 GGTGGAAACATT GGTGGAAAAATTTTATTTTACAGA GACAGCGTATGC ATTG (295) CATG (296) 439 chrX: chrX:AAAAGAAACTGA AAAAGAAACTGA 16 82 2.29 2.84E−08 3′ss CLL129771378-129790554 129771384-129790554 GGAATCAGTATC GGAATCAGCCTTACAGGCAGAAGC AGTATCACAGGC TCTG (303) AGAA (304) 440 chr1: chr1:TTCCCCATCAAC TTCCCCATCAAC 5 28 2.27 4.85E−06 3′ss CLL 19480448-1948141119480433-19481411 ATCAAAAGTTTT ATCAAAAGTTCC GTTGTCTGCAGT AATGGTGGCAGTTCCA (202) AAGA (203) 441 chr3: chr3: AAAATGGGCTCA AAAATGGGCTCA 10 522.27 1.39E−04 3′ss CLL 141896447-141900302 141896418-141900302GCAGTTAGGGTT GCAGTTAGACCT TTTTGTTGTTTG TTTCACAGATGC TTTG (741) TGCT(742) 442 chr1: chr1: AAGCACTGGCCC AAGCACTGGCCC 4 22 2.20 2.08E−02 3′ssCLL 156553242-156553591 156553242-156553588 AGTGTCAGGAGC AGTGTCAGAAGGCAGATTCTGTGC AGCCAGATTCTG GAGA (743) TGCG (744) 443 chr19: chr19:AGCCATTTATTT AGCCATTTATTT 11 53 2.17 2.14E−08 3′ss CLL 9728842-97301079728855-9730107 GTCCCGTGGGAA GTCCCGTGGGTT CCAATCTGCCCT TTTTTCCAGGGA TTTG(160) ACCA (161) 444 chr15: chr15: CCACTCTCACAA CCACTCTCACAA 1 8 2.171.41E−02 3′ss CLL 91448953-91449151 91448953-91449074 TGACCCAGGAGGTGACCCAGGCTG ACCCCCGGCGGC GATCAAGACCTT GCTT (745) TGAC (746) 445 chr1:chr1: TTGGAAGCGAAT TTGGAAGCGAAT 1 8 2.17 4.59E−02 3′ss CLL23398690-23399766 23398690-23399784 CCCCCAAGTCCT CCCCCAAGTGATTTGTTCTTTTGC GTATATCTCTCA AGTG (210) TCAA (211) 446 chr2: chr2:CCTTTACTTGGG AACCCGGAGAGA 1 8 2.17 4.13E−02 5′ss CLL 64457092-6447825264456774-64478252 GCTCTCAGCAAC AAAGGGAGCAAC TGATGTTGCCAT TGATGTTGCCATGCAG (747) GCAG (578) 447 chr14: chr14: GTGGGGGGCCAT GTGGGGGGCCAT 16 752.16 9.79E−09 3′ss CLL 23237380-23238985 23237380-23238999 TGCTGCATTTTGTGCTGCATGTAC TATTTTCCAGGT AGTCTTTGCCCG ACAG (122) CTGC (123) 448 chr15:chr15: ACTCAGATGCCG ACTCAGATGCCG 14 65 2.14 1.32E−05 3′ss CLL74326871-74327483 74326871-74327512 AAAACTCGCCCT AAAACTCGTGCACAGTCTGAGGTT TGGAGCCCATGG CTGT (748) AGAC (749) 449 chr10: chr10:GCCTACTCTTAA TCATCTTGAAAA 7 34 2.13 4.92E−03 exon CLL 89516679-8951945789516679-89527429 CCATTAGGGTGG ATGAAAATGTGG incl. ATAGGCATGTAGATAGGCATGTAG ACCT (750) ACCT (507) 450 chr20: chr20: TGGAGTGCGGATTGGAGTGCGGAT 2 12 2.12 4.37E−03 3′ss CLL 33703761-3370640033703736-33706400 TTGCAACACTTG TTGCAACAATCA CTTCCTTCTCCC AAGATCTGCGAGACAT (751) ACCA (752) 451 chr12: chr12: CAACTGGAGTTC CAACTGGAGTTC 12 532.05 3.67E−06 3′ss CLL 105514375-105514866 105514375-105514878ATTTTCAGGTTT ATTTTCAGACTA TTTGACAGACTA TGTATGAGCACT TGTA (753) TGGG(754) 452 chr1: chr1: CAATGTGTTGAC CAATGTGTTGAC 14 61 2.05 1.87E−03 3′ssCLL 155237988-155238083 155237937-155238083 CATCGCAGTCCC CATCGCAGCCTCCCTACAGCCCTG TCCTGCCAACTT TTCA (755) ACAG (756) 453 chr15: chr15:CAGCTGCTCTCA CAGCTGCTCTCA 16 67 2.00 7.47E−04 3′ss CLL 89870310-8987039789870294-89870397 GGAGAGAGTGGA GGAGAGAGGTAC CTGGCTCTGTAG AAAGAAGACCCCGTAC (757) TGGC (758) 454 chr3: chr3: TCTCTAGTGGGC TCTCTAGTGGGC 8 352.00 7.53E−03 3′ss CLL 141272782-141274647 141272782-141274681CCTTCTAGTTCT CCTTCTAGGAAT ACAAGGTAAAAC GACCAAAAGAAG TCTA (759) ACAA(760) 455 chr1: chr1: AGCTCCGAGAGG AGCTCCGAGAGG 2 11 2.00 6.28E−03 3′ssCLL 202122978-202123313 202122963-202123313 GCAAGGAGCTCC GCAAGGAGAAATCTCCCTCCTAGA GTGTCCACTACT AATG (761) GGCC (762) 456 chrX: chrX:GACGTGGCAGCT GACGTGGCAGCT 19 73 1.89 1.20E−04 3′ss CLL 47315813-4732680847315797-47326808 CATGTGAGCATT CATGTGAGGCTT GTGTCGTTACAG CAGTGTCATTTGGCTT (763) AGGA (764) 457 chr6: chr6: AAGGAAGAACAA AATGTTAAGGAG 2 101.87 4.93E−04 exon CLL 25975158-25983391 25973513-25983391 GACTTTGTTTAGTCATCAAGTTAG incl. TGTGACTCTGGA TGTGACTCTGGA TCCA (765) TCCA (766) 458chr11: chr11: AGGAGAACACCT AGGAGAACACCT 15 55 1.81 1.53E−04 3′ss CLL10876665-10877690 10876633-10877690 TATTTCAGCTTT TATTTCAGAAAATATTTTTATGTG GGTGTACCATAC ATAA (767) CTGA (768) 459 chr9: chr9:CTGATGAAAACT CTGATGAAAACT 12 43 1.76 4.16E−05 3′ss CLL 93641235-9364812793641235-93650030 ACTACAAGACAC ACTACAAGGCCC CTTACAGGCCAG AGACCCATGGAAGAGA (769) AGTG (723) 460 chr8: chr8: GGGGCCACCAGG GGGGCCACCAGG 21 721.73 2.11E−05 3′ss CLL 145313817-145314126 145313817-145314142TTGGCCAGCGGC TTGGCCAGGGCC CCCCTTTCCCAG ATGGCTGAGCAC GGCC (770) GCAG(771) 461 chr7: chr7: TGCACACGCCTC TGCACACGCCTC 4 15 1.68 2.26E−02 3′ssCLL 98579583-98580862 98579583-98580886 TCCTACAGAGTC TCCTACAGGCAGTCTTATGCTGGT CCCAGCAAATCA CCCA (772) TCGA (773) 462 chr22: chr22:GAGCTGGAGAGG GAGCTGGAGAGG 14 46 1.65 2.74E−04 3′ss CLL 50660983-5066256950661021-50662569 AAGGCGAGAGGC AAGGCGAGGCAG AGCTCGTCGGGA GCACTGGTCGACGCAG (774) CACT (775) 463 chr6: chr6: GCCCCCGTTTTC GCCCCCGTTTTC 17 551.64 1.17E−04 3′ss CLL 31936315-31936399 31936315-31936462 CTGCCCAGCCCTCTGCCCAGTACC TGTCCTCAGTGC TGAAGCTGCGGG ACCC (307) AGCG (308) 464 chr7:chr7: CCGCCTCTGCCT CCGCCTCTGCCT 8 26 1.58 3.53E−03 3′ss CLL64139714-64150776 64139714-64144464 TCGGATAGGTCT TCGGATAGGAAAGGCCCCACCCTG GGTTGAAAGAGC GAGT (776) CAAC (777) 465 chr12: chr12:TTTCTCATATTG TTTCTCATATTG 5 17 1.58 4.42E−03 3′ss CLL 51174021-5118968051174021-51189691 CTCAACAGTTCT CTCAACAGGTAT TTTTTAGGTATC CATCTTTATCAGATCT (778) AAAG (779) 466 chr11: chr11: AGTGGCTTTGGC AGTGGCTTTGGC 15 461.55 1.99E−03 intron CLL 126144916-126144918 126144916-126145221GTCTTATGGAGG GTCTTATGGGAT reten- CTTGCTTGCAGA GGAGGACGAAGG tion GGGG(780) TTGG (781) 467 chr1: chr1: CATAGTGGAAGT CATAGTGGAAGT 20 60 1.546.97E−06 3′ss CLL 67890660-67890765 67890642-67890765 GATAGATCTTCTGATAGATCTGGC TTTTCACATTAC CTGAAGCACGAG AGTG (444) GACA (445) 468 chr1:chr1: GGTGACACTCAA GGTGACACTCAA 22 65 1.52 1.10E−05 3′ss CLL157771381-157771704 157771367-157771704 CTTCACAGGTCT CTTCACAGTGCCCTCCCTCTAGTG TACTGGGGCCAG CCTA (782) AAGC (783) 469 chr2: chr2:GGCAACTTCGTT GGCAACTTCGTT 27 76 1.46 7.08E−07 3′ss CLL106781255-106782511 106781240-106782511 AATATGAGCTTT AATATGAGGTCTCTACTCAACAGG ATCCAGGAAAAT TCTA (375) GGTG (376) 470 chr14: chr14:CGCTCTCCGCCT AGGGAGACGTTC 19 54 1.46 2.09E−04 exon CLL 75348719-7535228875349327-75352288 TCCAGAAGGGGT CCTGCCTGGGGT skip CTCCTTATGCCACTCCTTATGCCA GGGA (208) GGGA (209) 471 chr2: chr2: TTTCCATTGGGCGAGGGCCACCAA 3 10 1.46 4.35E−02 exon CLL 153551136-153571063153551136-153572508 CAATCAAGATGC TGGGACAAATGC incl. CTGGAATGATGTCTGGAATGATGT CGTC (784) CGTC (785) 472 chrX: chrX: AGAGACAAAGAGAGAGACAAAGAG 33 92 1.45 4.85E−06 3′ss CLL 118759359-118763280118759342-118763280 AAGAAAAACTCT AAGAAAAATTAA TACTGTTTTACA CTCTGCTGTTTGGTTA (786) CTGC (787) 473 chr17: chr17: CTCACCAGCGCC CTCACCAGCGCC 5 151.42 1.43E−03 exon CLL 27238402-27239499 27238255-27239499 ATCGTCAGCTCTATCGTCAGATGG incl. AGGAGTTCCAGA CAAGGTCAGCCC GCCT (788) CGGC (789) 474chr12: chr12: ATCAGGTGCTCA ATCAGGTGCTCA 11 30 1.37 9.13E−04 3′ss CLL50821692-50822699 50821692-50822717 TCCTGAGGTGTC TCCTGAGGGTAATGTCTTTAATAC TGCAGAGCTCTC AGGT (790) AGAA (791) 475 chr6: chr6:TCTGGCAGCCCA TCTGGCAGCCCA 17 45 1.35 1.98E−04 3′ss CLL 43152643-4315322843152643-43153193 CGATGCTGCAAG CGATGCTGGGAG ATGGCATCGAGC TCGGGCTCACGTAGCA (792) CCTT (793) 476 chr3: chr3: AGAATTTTAAGA AGAATTTTAAGA 11 291.32 1.64E−03 3′ss CLL 3186394-3188099 3186394-3188113 TACTTCAGATTTTACTTCAGGTTT TGTCTTGTAGGT TATGGGAGAATT TTTA (794) GTAG (795) 477 chr7:chr7: CCGCCTCTGCCT CCGCCTCTGCCT 1 4 1.32 2.43E−02 3′ss CLL64139714-64150765 64139714-64144464 TCGGATAGGCTT TCGGATAGGAAATATTTAGGTCTG GGTTGAAAGAGC GCCC (796) CAAC (777) 478 chr3: chr3:GAGCTAGTCAGA AAATTCTTGACC 15 38 1.29 1.66E−02 exon CLL 56606456-5662699756605330-56626997 CTTTAGAGGAAA AATCTAGGGAAA incl. CAGTACTGCTGGCAGTACTGCTGG AGCA (797) AGCA (798) 479 chr22: chr22: CTTCATCTGTGGCTTCATCTGTGG 25 61 1.25 5.02E−06 3′ss CLL 24043032-2404761524037704-24047615 ATAAGCAGGTCA ATAAGCAGTGCA TGTCCTCCAGGT GGCCAAGGCCCCTTCT (799) CTGC (800) 480 chr17: chr17: CCGGAGCCCCTT CCGGAGCCCCTT 8 201.22 1.07E−02 3′ss CLL 45229302-45232037 45229284-45232037 CAAAAAAGACTTCAAAAAAGTCTG TTCGTGTTTTAC TTGCCAGAATCG AGTC (327) GCCA (328) 481 chr1:chr1: AGTATGGGATAT TCATTCTTATTT 8 20 1.22 2.03E−02 exon CLL62149218-62152463 62149218-62160368 TTTAAAAGATTG CAATGCAGATTG incl.TTGGACCTTCAG TTGGACCTTCAG ATGG (801) ATGG (802) 482 chr22: chr22:CTTTATCTGTGC CTTCATCTGTGG 31 73 1.21 1.26E−05 exon CLL 24037704-2404291224037704-24047615 ATGAACAGTGCA ATAAGCAGTGCA incl. GGCCAAGGCCCCGGCCAAGGCCCC CTGC (803) CTGC (800) 483 chr7: chr7: AAGTCGTCCTCTAGAGAGAAACAT 18 42 1.18 2.78E−02 exon CLL 104844232-104909252104844232-105029094 TCAGAAAGGCCG CCGAAAAAGCCG incl. GAGCCTCAACAGGAGCCTCAACAG AAAG (804) AAAG (805) 484 chr2: chr2: TGGGCTACCTTATGGGCTACCTTA 23 53 1.17 3.28E−02 exon CLL 85779690-8578006185779104-85780061 ACCCTGGGGTAT ACCCTGGGGATT incl. TTACACAGAGTCTTTGACCCTCGT GGCG (806) GTGG (807) 485 chr1: chr1: GACTGCCCTAAAGACTGCCCTAAA 10 23 1.13 4.92E−03 3′ss CLL 52902647-5290389152902635-52903891 AGGAAAAGTTTA AGGAAAAGACTA CTGTTTAGACTA AAGAAGAAAGACAAGA (808) AGTG (809) 486 chr3: chr3: TGATAGTTGGAG TGATAGTTGGAG 11 251.12 3.47E−03 3′ss CLL 179065598-179066635 179065598-179066632CGGAGACTCATA CGGAGACTTAGC ATGGCAGAACCT ATAATGGCAGAA GTTT (810) CCTG(811) 487 chr1: chr1: TCATTCTTATTT TCATTCTTATTT 5 12 1.12 3.19E−02 exonCLL 62152593-62160368 62149218-62160368 CAATGCAGAGAC CAATGCAGATTG incl.AGGGTCTTGCTC TTGGACCTTCAG TGTT (812) ATGG (802) 488 chr19: chr19:TGACGGTGCCAC TGACGGTGCCAC 30 65 1.09 4.13E−02 exon CLL 53935281-5393683253935281-53945048 CGCGGCGCTTTT CGCGGCGCAGAG incl. CTCCCTTAGATGGAGTCTGCAATG CCTT (813) CCGA (814) 489 chr19: chr19: GCAGTGGCTGGAGCAGTGGCTGGA 42 85 1.00 4.02E−05 3′ss CLL 19414656-1941665719414721-19416657 GATCAAAGTTTC GATCAAAGAGAG ACCCCCAGAGGG AGTGTGCCTATTAGCC (815) GACT (816) 490 chrX: chrX: GGACGATGGGGA GGACGATGGGGA 3 7 1.008.68E−03 3′ss CLL 47103949-47104083 47103949-47104080 TGAGAAAGATGATGAGAAAGAAGA CGAGGAGGATAA TGACGAGGAGGA AGAT (817) TAAA (818) 491 chr5:chr5: ACTCTTATGCAG ACTCTTATGCAG 24 48 0.97 7.63E−03 3′ss CLL1579599-1585098 1581810-1585098 TCCCCATGGACT TCCCCATGAGGA GAACCATCAAGAGATCCTAGTCTC CACC (819) ACCA (531) 492 chr17: chr17: GACCCATGCATCGACCCATGCATC 47 93 0.97 2.22E−02 3′ss CLL 73587327-7358768173587327-73587696 CTCCTGTGCTCC CTCCTGTGTGGG TCCCACTGCAGT CACAGTGGCTCAGGGC (820) GGGA (821) 493 chr18: chr18: CCAAGTTTTGTG CCAAGTTTTGTG 38 750.96 7.90E−03 3′ss CLL 224200-224923 224179-224923 AAAGAAAGTGTAAAAGAAAGAACA TGTTTTGTTCAC TCAGATACCAAA GACA (116) CCTA (117) 494 chr16:chr16: CATCAAGCAGCT CATCAAGCAGCT 10 20 0.93 2.86E−02 3′ss CLL57473207-57474683 57473246-57474683 GTTGCAATGTTT GTTGCAATCTGCAGTCCCAGGAAG CCACAAAGAATC CACC (822) CAGC (823) 495 chr7: chr7:TGAGAGTCTTCA TGAGAGTCTTCA 45 86 0.92 7.69E−08 3′ss CLL 99943591-9994733999943591-99947421 GTTACTAGTTTG GTTACTAGAGGC TCTTTCCTAGAT GGATTTCCCTGACCAG (420) CTGA (421) 496 chr12: chr12: CAATCATTGACA CAATCATTGACA 29 540.87 3.27E−02 3′ss CLL 47599928-47600293 47599852-47600293 ATATTATGACCCATATTATGGAAC TGCATGTGATGG TGACTCAGCGCA ATCA (824) AGAA (825) 497 chr9:chr9: GGGACACTGTGC GGGACACTGTGC 43 72 0.73 1.74E−02 3′ss CLL140633231-140637822 140633231-140637843 CGAATGAACTTG CGAATGAACAGCCTTGCCTTTTGT TGCAGTATCTCG TTTA (826) GAAG (827) 498 chr19: chr19:TCAGGGGGCGCG TCGAGCCAGGCT 10 17 0.71 2.37E−02 exon CLL 17654242-1765749417654440-17657494 TGCTGAAGGAGC GCAAAAAGGAGC skip TGCCTGAGTTCGTGCCTGAGTTCG AGGG (828) AGGG (829) 499 chr6: chr6: CTACAACCAGAGCTACAACCAGAG 57 92 0.68 2.50E−03 3′ss CLL 29691704-2969194929691704-29691966 CGAGGCTGGGTC CGAGGCTGGGAA TCACACCCTCCA TGAATGGCTGCGGGGA (830) ACAT (831) 500 chr20: chr20: TGCCTAAGGCGG TGCCTAAGGCGG 54 870.68 4.59E−02 3′ss CLL 30310151-30310420 30310133-30310420 ATTTGAATCTCTATTTGAATAATC TTCTCTCCCTTC TTATCTTGGCTT AGAA (479) TGGA (480) 501 chr4:chr4: TCCAACAAGCAC TCCAACAAGCAC 55 87 0.65 1.64E−04 3′ss CLL17806394-17806729 17806379-17806729 CTCTGAAGTCTT CTCTGAAGGTTACTCATTCACAGG AGGCTACCTTTC TTAA (832) CAGA (833) 502 chr9: chr9:CACCACAAAATC CACCACAAAATC 41 65 0.65 4.07E−03 3′ss CLL140622981-140637822 140622981-140637843 ACAGACAGCTTG ACAGACAGCAGCCTTGCCTTTTGT TGCAGTATCTCG TTTA (458) GAAG (459) 503 chr1: chr1:GAATCCGTATCT GAATCCGTATCT 45 70 0.63 4.59E−02 3′ss CLL155278756-155279833 155278756-155279854 GGGAACAGAGCC GGGAACAGAATGCTTTGCTCCTCC AACGGAGACCAG CTCA (432) AATT (433) 504 chr17: chr17:GTTCCCGAGGCT GTTCCCGAGGCT 60 90 0.58 8.49E−05 3′ss CLL 40690773-4069296740690773-40695045 GTCACCAGGGTG GTCACCAGTGGA TTCCCTCAGGTC TACTGAGGCTGTAATG (834) GTGG (835) 505 chr12: chr12: ATTTCCAGAGGA ATTTCCAGAGGA 51 760.57 1.45E−05 3′ss CLL 95660408-95663814 95660408-95663826 TTTACACTTTTGTTTACACTGGTC CTTGACAGGGTC AGTGCTGCTTGC AGTG (462) CCAT (463) 506 chr3:chr3: CCAGATCAACAC CCAGATCAACAC 44 65 0.55 2.77E−02 3′ss CLL133371473-133372188 133371458-133372188 AATTGATAGTCG AATTGATAATGTTACTCTTTCAGA CAGCAATATTTC TGTC (836) CAAC (837) 507 chr19: chr19:CGTCCTGCCCCC CGTCCTGCCCCC 67 94 0.48 2.30E−02 3′ss CLL 7075116-70756657075116-7075686 AACTGCCGCTCT AACTGCCGCCTC GTCTTCCCTGTT TCAGCGAGAAGG CCCA(838) ACAC (839) 508 chr10: chr10: TGACGTTCTCTG TGACGTTCTCTG 53 74 0.472.22E−03 3′ss CLL 75554088-75554298 75554088-75554313 TGCTCCAGTGGTTGCTCCAGGTTC TTCTCCCACAGG CCGGCCCCCAAG TTCC (466) TCGC (467) 509 chr19:chr19: TGCAGGGGGAGC TGCAGGGGGAGC 48 66 0.45 6.62E−03 3′ss CLL11558433-11558507 11558433-11558537 AGCCCAAGGAGG AGCCCAAGCCGGCCCCACCGCCAC CCAGCCCTGCTG TGTC (840) AGGA (841) 510 chr1: chr1:GACTGCCCTAAA GACTGCCCTAAA 55 74 0.42 8.74E−03 3′ss CLL 52902650-5290389152902635-52903891 AGGAAAAGCAGT AGGAAAAGACTA TTACTGTTTAGA AAGAAGAAAGACCTAA (842) AGTG (809) 511 chr17: chr17: CTATGAGGCCAT GTTCCCGAGGCT 68 870.35 1.45E−03 exon CLL 40693224-40695045 40690773-40695045 GACTGCAGTGGAGTCACCAGTGGA incl. TACTGAGGCTGT TACTGAGGCTGT GTGG (843) GTGG (835) 512chr5: chr5: CTTCTCAAGATC CTTCTCAAGATC 70 86 0.29 2.73E−02 3′ss CLL139865317-139866542 139865317-139866590 AGTCTCAGGTGC AGTCTCAGGAACCACGTGTGCCAA CTGACAGAACTT CGCA (844) CACA (845) 513 chr6: chr6:ACCTTAACAAGA AATCACTAGGAA 58 71 0.29 1.38E−02 exon CLL127636041-127637594 127636041-127648146 TTTATGAGACTT CTCCAGAGACTT incl.CCTTTAATAAGT CCTTTAATAAGT GTTG (846) GTTG (847) 514 chr4: chr4:ACTGGGCTTCCA ACTGGGCTTCCA 60 72 0.26 4.54E−02 exon CLL 54266006-5428078154266006-54292038 CCGAGCAGAAAC CCGAGCAGGAGA incl. AGCACTTCTTCTTTACCTGGGGCA CAGT (848) ATTG (849) 515 chr9: chr9: CTGAAGACGGGACTGAAGACGGGA 87 92 0.08 2.80E−02 3′ss CLL 130566979-130569251130566979-130569270 TTCTTTAGCTCT TTCTTTAGGTTC CCCCACCTGGTG GGGAGCGGATCCCAGG (850) GCAT (851) 516 chr17: chr17: ATCTCAGGAGCA CCCACCCCTTCA 93 980.07 4.18E−03 5′ss CLL 72759659-72763074 72760785-72763074 CCTGAATGGTCCCCCTGCAGGTCC CCTGCCTGTGCC CCTGCCTGTGCC CTTC (852) CTTC (853) 517 chr2:chr2: AGCAAGTAGAAG AGCAAGTAGAAG 0 72 6.19 1.51E−10 3′ss Mel.109102364-109102954 109102364-109102966 TCTATAAAATTT TCTATAAAATACACCCCCAGATAC AGCTGGCTGAAA AGCT (1) TAAC (2) 518 chr19: chr19:GGCCCTTTTGTC GGCCCTTTTGTC 0 72 6.19 7.67E−09 3′ss Mel. 57908542-5790978057908542-57909797 CTCACTAGCATT CTCACTAGGTTC TCTGTTCTGACA TTGGCATGGAGCGGTT (7) TGAG (8) 519 chr2: chr2: TGACCACGGAGT TGACCACGGAGT 0 59 5.911.12E−08 3′ss Mel. 232196609-232209660 232196609-232209686 ACCTGGGGCCCTACCTGGGGATCA TTTTTCTCTTTC TGACCAACACGG CTTC (37) GGAA (38) 520 chr1:chr1: CAAGTATATGAC CAAGTATATGAC 0 56 5.83 3.98E−05 3′ss Mel.245246990-245288006 245246990-245250546 TGAAGAAGATCC TGAAGAAGGTGATGAATTCCAGCA GCCTTTTTCTCA AAAC (21) AGAG (22) 521 chr11: chr11:GGCCACACGCCT GGCCACACGCCT 0 54 5.78 1.58E−06 3′ss Mel. 65635911-6563598065635892-65635980 CTGCCAAGCCCC CTGCCAAGACAT TCTCCCCTGGCA TGATGAGTGTGACAGA (854) GTCT (855) 522 chr3: chr3: TGCAGTTTGGTC TGCAGTTTGGTC 0 495.64 5.19E−07 3′ss Mel. 9960293-9962150 9960293-9962174 AGTCTGTGCCTTAGTCTGTGGGCT CCTCACCCCTCT CTGTGGTATATG CCTC (23) ACTG (24) 523 chr3:chr3: GAGTACGAGGTC GAGTACGAGGTC 0 48 5.61 2.52E−15 3′ss Mel.48457878-48459319 48457860-48459319 TCCAGCAGCCTG TCCAGCAGCCTCCCCTGTGCCTAC GTGTGCATCACC AGCC (856) GGGG (857) 524 chr10: chr10:TACCTCTGGTTC TACCTCTGGTTC 0 47 5.58 5.54E−06 3′ss Mel. 99214556-9921539599214556-99215416 CTGTGCAGTCTT CTGTGCAGTTCT CGCCCCTCTTTT GTGGCACTTGCCCTTA (13) CTGG (14) 525 chr1: chr1: TCTTTGGAAAAT TCTTTGGAAAAT 0 45 5.523.06E−06 3′ss Mel. 101458310-101460665 101458296-101460665 CTAATCAATTTTCTAATCAAGGGA CTGCCTATAGGG AGGAAGATCTAT GAAG (25) GAAC (26) 526 chr9:chr9: AGCGCATCGCAG AGCGCATCGCAG 0 45 5.52 1.42E−03 3′ss Mel.90582559-90584108 90582574-90584108 CTTCCAAGTACT CTTCCAAGGCTCTCTTCACAGCTC TCCTCCATCAGT CCCT (858) ACTT (859) 527 chr1: chr1:TCACTCAAACAG TCACTCAAACAG 0 44 5.49 1.90E−07 3′ss Mel.179835004-179846373 179834989-179846373 TAAACGAGTTTT TAAACGAGGTATATCATTTACAGG GTGACGCATTCC TATG (53) CAGA (54) 528 chr14: chr14:AGTTAGAATCCA AGTTAGAATCCA 0 41 5.39 4.30E−08 3′ss Mel. 74358911-7436047874358911-74360499 AACCAGAGTGTT AACCAGAGCTCC GTCTTTTCTCCC TGGTACAGTTTGCCCA (61) TTCA (62) 529 chr11: chr11: TGGGCAGCCCCC TGGGCAGCCCCC 0 395.32 2.61E−02 3′ss Mel. 117167925-117186250 117167677-117186250CGCAGACGTTGG CGCAGACGCTCA TTTTTCAGCAGA ACATCCTGGTGG CCTG (860) ATAC(861) 530 chr20: chr20: AGAACTGCACCT AGAACTGCACCT 0 36 5.21 6.58E−073′ss Mel. 62701988-62703210 62701988-62703222 ACACACAGCCCT ACACACAGGTGCGTTCACAGGTGC AGACCCGCAGCT AGAC (29) CTGA (30) 531 chr18: chr18:AGAAAGAGCATA AGAAAGAGCATA 0 33 5.09 6.82E−09 3′ss Mel. 33605641-3360686233573263-33606862 AATTGGAAATAT AATTGGAAGAGT TGGACATGGGCG ACAAGCGCAAGCTATC (91) TAGC (92) 532 chr3: chr3: AACCAAGAGGAC AACCAAGAGGAC 0 32 5.041.83E−02 3′ss Mel. 52283338-52283671 52283338-52283685 CCACACAGGATGCCACACAGGTTC GTCTTCACAGGT TCAAAGCTGGCC TCTC (862) CAGA (863) 533 chr9:chr9: AAATGAAGAAAC AAATGAAGAAAC 0 32 5.04 6.82E−09 3′ss Mel.125759640-125760854 125759640-125760875 TCCTAAAGCCTC TCCTAAAGATAATCTCTTTCTTTG AGTCCTGTTTAT TTTA (67) GACC (68) 534 chr12: chr12:AATATTGCTTTA AATATTGCTTTA 0 31 5.00 9.14E−06 3′ss Mel.116413154-116413319 116413118-116413319 CCAAACAGGGAC CCAAACAGGTCACCCTTCCCCTTC CGGAGGAGTAAA CCCA (77) GTAT (78) 535 chr18: chr18:TTGGACCGGAAA TTGGACCGGAAA 1 62 4.98 1.13E−06 3′ss Mel. 683395-685920683380-685920 AGACTTTGAGTC AGACTTTGATGA TCTTTTTGCAGA TGGATGCCAACC TGAT(15) AGCG (16) 536 chr1: chr1: ATCAGAAATTCG ATCAGAAATTCG 0 29 4.918.06E−03 3′ss Mel. 212515622-212519131 212515622-212519144 TACAACAGGTTTTACAACAGCTCC CTTTTAAAGCTC TGGAGCTTTTTG CTGG (65) ATAG (66) 537 chr1:chr1: CTCAGAGCCAGG CTCAGAGCCAGG 0 29 4.91 3.06E−05 3′ss Mel.35871069-35873587 35871069-35873608 CTGTAGAGATGT CTGTAGAGTCCGTTTCTACCTTTC CTCTATCAAGCT CACA (105) GAAG (106) 538 chrX: chrX:GTCTTGAGAATT ACTTCCTTAGTG 0 29 4.91 1.16E−06 5′ss Mel. 47059943-4706029247059013-47060292 GGAAGCAGGTGG GTTTCCAGGTGG TGGTGCTCACCA TGGTGCTCACCAACAC (113) ACAC (112) 539 chr2: chr2: AAATTTAACATT AAATTTAACATT 0 284.86 3.75E−06 3′ss Mel. 24207701-24222524 24207701-24222541 ACTCATAGTTTTACTCATAGAGTA TGCTGTTTTACA AGCCATATCAAA GAGT (546) GACT (547) 540 chr5:chr5: CTCCATGCTCAG CTCCATGCTCAG 0 28 4.86 8.03E−04 3′ss Mel.869519-870587 865696-870587 CTCTCTGGTTTC CTCTCTGGGGAA TTTCAGGGCCTGGGTGAAGAAGGA CCAT (128) GCTG (129) 541 chr20: chr20: ACATGAAGGTGGACATGAAGGTGG 0 27 4.81 4.86E−06 3′ss Mel. 34144042-3414472534144042-34144743 ACGGAGAGGCTC ACGGAGAGGTAC CCCTCCCACCCC TGAGGACAAATCAGGT (49) AGTT (50) 542 chr2: chr2: TGGGAGGAGCAT TGGGAGGAGCAT 0 27 4.811.72E−04 3′ss Mel. 97285513-97297048 97285499-97297048 GTCAACAGAGTTGTCAACAGGACT TCCCTTATAGGA GGCTGGACAATG CTGG (9) GCCC (10) 543 chr19:chr19: AGCCATTTATTT AGCCATTTATTT 1 54 4.78 1.18E−09 3′ss Mel.9728842-9730107 9728855-9730107 GTCCCGTGGGAA GTCCCGTGGGTT CCAATCTGCCCTTTTTTCCAGGGA TTTG (160) ACCA (161) 544 chr15: chr15: ATATTCCTTTTAATATTCCTTTTA 0 25 4.70 3.65E−06 3′ss Mel. 49420970-4942167349420957-49421673 TTTCTAAGTCTT TTTCTAAGGAGT TTGTCTTAGGAG TAAACATAGATGTTAA (864) TAGC (865) 545 chr12: chr12: ATTTGGACTCGC ATTTGGACTCGC 1 494.64 6.42E−06 3′ss Mel. 105601825-105601935 105601807-105601935TAGCAATGATGT TAGCAATGAGCA CTGTTTATTTTT TGACCTCTCAAT AGAG (41) GGCA (42)546 chr14: chr14: AGATGTCAGGTG AGATGTCAGGTG 0 24 4.64 2.35E−03 3′ss Mel.75356052-75356580 75356052-75356599 GGAGAAAGCCTT GGAGAAAGCTGTTGATTGTCTTTT TGGAGACACAGT CAGC (89) TGCA (90) 547 chr11: chr11:CATAAAATTCTA CATAAAATTCTA 0 23 4.58 4.56E−05 3′ss Mel. 4104212-41044714104212-4104492 ACAGCTAATTCT ACAGCTAAGCAA CTTTCCTCTGTC GCACTGAGCGAG TTCA(69) GTGA (70) 548 chr15: chr15: GAAACCAACTAA GAAACCAACTAA 0 23 4.582.75E−04 3′ss Mel. 59209219-59224554 59209198-59224554 AGGCAAAGCCCAAGGCAAAGGTAA TTTTCCTTCTTT AAAACATGAAGC CGCA (101) AGAT (102) 549 chr22:chr22: CTGGGAGGTGGC CTGGGAGGTGGC 0 23 4.58 1.03E−06 3′ss Mel.19044699-19050714 19044675-19050714 ATTCAAAGCCCC ATTCAAAGGCTCACCTTTTGTCTC TTCAGAGGTGTT CCCA (45) CCTG (46) 550 chr3: chr3:CACTGCTGGGAG CACTGCTGGGAG 0 23 4.58 5.29E−10 3′ss Mel.129284872-129285369 129284860-129285369 AGTGGAAGTTGC AGTGGAAGATTCTTCCACAGATTC CTGAGAGCTGCC CTGA (524) GGCC (525) 551 chr9: chr9:GGTCCTGAACGC GGTCCTGAACGC 0 23 4.58 1.89E−04 3′ss Mel.138903859-138905044 138903870-138905044 TGTGAAATAACT TGTGAAATTGTATCGCCCCCAGCT CTGTCAGAACTT TCAA (866) CGCC (867) 552 chr6: chr6:TGGAGCAGTATG TGGAGCAGTATG 0 22 4.52 8.93E−03 3′ss Mel. 35255622-3525802935255622-35258042 CCAGCAAGACTT CCAGCAAGGTTC TTCCCCCAGGTT TTCATGACAGCCCTTC (868) AGAT (869) 553 chr8: chr8: TCGTGCAGACCC TCGTGCAGACCC 0 224.52 3.21E−11 3′ss Mel. 28625893-28627405 28625839-28627405 TGGAGAAGATCTTGGAGAAGCATG CACAGATGTGCA GCTTCAGTGATA GTCT (870) TTAA (871) 554 chr6:chr6: CCGGGGCCTTCG CCGGGGCCTTCG 2 67 4.50 2.74E−12 3′ss Mel.10723474-10724788 10723474-10724802 TGAGACCGCTTG TGAGACCGGTGCTTTTCTGCAGGT AGGCCTGGGGTA GCAG (95) GTCT (96) 555 chr4: chr4:GTGCCAACGAGG GTGCCAACGAGG 2 65 4.46 9.90E−07 3′ss Mel.184577127-184580081 184577114-184580081 ACCAGGAGTTCT ACCAGGAGATGGTTATTTCAGATG AACTAGAAGCAT GAAC (734) TACG (735) 556 chr22: chr22:CTCTCTCCAACC CTCTCTCCAACC 0 21 4.46 4.84E−04 3′ss Mel. 39064137-3906687439064137-39066888 TGCATTCTCATC TGCATTCTTTGG TCGCCCACAGTT ATCGATCAACCCGGAT (140) GGGA (141) 557 chr9: chr9: TTGAAGCTCAGT TTGAAGCTCAGT 0 214.46 3.30E−03 3′ss Mel. 37501841-37503015 37501841-37503039 GAGAAAAGTTCTGAGAAAAGGATG TCTGTTTATGTC ATGGAGATAGCC TTCC (872) AAAG (873) 558 chr14:chr14: CAGTTATAAACT CAGTTATAAACT 0 20 4.39 2.55E−03 3′ss Mel.71059726-71060012 71059705-71060012 CTAGAGTGAGTT CTAGAGTGCTTATATTTTCCTTTT CTGCAGTGCATG ACAA (79) GTAT (80) 559 chr17: chr17:GGAGCAGTGCAG GGAGCAGTGCAG 0 20 4.39 2.74E−12 3′ss Mel. 71198039-7119916271198039-71199138 TTGTGAAATCAT TTGTGAAAGTTT TACTTCTAGATG TGATTCATGGATATGC (31) TCAC (32) 560 chr9: chr9: CGCCCTGACACA CGCCCTGACACA 0 20 4.391.26E−04 3′ss Mel. 35608506-35608842 35608506-35608858 CAATCAGGACTTCAATCAGGGCTC CTCTATCTACAG TGTTGCAAGAGG GCTC (874) GGGT (875) 561 chrX:chrX: ACTTCCTTAGTG ACTTCCTTAGTG 0 20 4.39 2.32E−03 3′ss Mel.47059013-47059808 47059013-47060292 GTTTCCAGGTTG GTTTCCAGGTGGCCAGGGCACTGC TGGTGCTCACCA AGCT (111) ACAC (112) 562 chr12: chr12:CTTGGAGCTGAC CTTGGAGCTGAC 4 96 4.28 5.10E−13 3′ss Mel.107378993-107380746 107379003-107380746 GCCGACGGGGAA GCCGACGGTTTACTGACAAGATCA TTGCAGGGAACT CATT (130) GACA (131) 563 chr10: chr10:TTGCTGGCCATC TTGCTGGCCATC 0 18 4.25 1.13E−14 3′ss Mel.133782836-133784141 133782073-133784141 GGATTGGGCCCT GGATTGGGGATCTCGTTTCAGGAT TATATTGGAAGG GGAT (876) CGTC (877) 564 chr11: chr11:CCACCGCCATCG CCACCGCCATCG 0 18 4.25 6.04E−04 3′ss Mel. 64877395-6487793464877395-64877953 ACGTGCAGTACC ACGTGCAGGTGG TCTTTTTACCAC GGCTCCTGTACGCAGG (167) AAGA (168) 565 chr21: chr21: ATCATAGCCCAC ATCATAGCCCAC 1 354.17 1.72E−04 3′ss Mel. 37416267-37417879 37416254-37417879 ATGTCCAGTTTTATGTCCAGGTAA TCTTTCTAGGTA AAGCAGCGTTTA AAAG (695) ATGA (696) 566 chr15:chr15: TGATTCCAAGCA TGATTCCAAGCA 1 34 4.13 1.03E−06 3′ss Mel.25213229-25219533 25213229-25219457 AAAACCAGCCTT AAAACCAGGCTCCCCCTAGGTCTT CATCTACTCTTT CAGA (230) GAAG (231) 567 chr17: chr17:TACTGAAATGTG TACTGAAATGTG 0 16 4.09 5.46E−04 3′ss Mel. 34942628-3494345434942628-34943426 ATGAACATATCC ATGAACATATCC AGGTAATCGAGA AGAAGCTTGGAAGACC (124) GCTG (125) 568 chr2: chr2: CCATTCGAGAGC CCATTCGAGAGC 0 164.09 2.25E−03 3′ss Mel. 219610954-219611752 219610954-219611725ATCAGAAGATTG ATCAGAAGCTAA GGAGGAAGGACC ACCATTTCCCAG GGCT (878) GCTC(879) 569 chr10: chr10: TCTTGCCAGAGC TCTTGCCAGAGC 0 15 4.00 9.94E−073′ss Mel. 99219232-99219415 99219283-99219415 TGCCCACGCTCT TGCCCACGCTTCCCACCCTCAGCT TTTCCTTGCTGC GCCT (587) TGGA (588) 570 chr11: chr11:AGATCGCCTGGC AGATCGCCTGGC 0 15 4.00 9.65E−05 3′ss Mel. 3697619-36977383697606-3697738 TCAGTCAGTTTT TCAGTCAGACAT TCTCTCTAGACA GGCCAAACGTGT TGGC(187) AGCC (188) 571 chr11: chr11: CGGCGCGGGCAA CGGCGCGGGCAA 0 15 4.004.00E−05 3′ss Mel. 62648919-62649352 62648919-62649364 CCTGGCGGCCCCCCTGGCGGGTCT CATTTCAGGTCT GAAGGGGCGTCT GAAG (165) CGAT (166) 572 chr1:chr1: TCAGGAGCAGAG CTCAGGGAAGGG 0 15 4.00 2.96E−02 5′ss Mel.113195986-113196219 113192091-113196219 AGGAAAAGTGCA GCAGCACATGCATTTGCCCAGTAT TTTGCCCAGTAT AACA (880) AACA (881) 573 chr1: chr1:CGATCTCCCAAA CGATCTCCCAAA 0 15 4.00 5.55E−03 3′ss Mel. 52880319-5288041252880319-52880433 AGGAGAAGTCTG AGGAGAAGCCCC ACCAGTCTTTTC TCCCCTCGCCGATACA (55) GAAA (56) 574 chr15: chr15: TCACACAGGATA GCCTCACTGAGC 1 303.95 6.03E−06 exon Mel. 25212299-25213078 25207356-25213078 ATTTGAAAGTGTAACCAAGAGTGT incl. CAGTTGTACCCG CAGTTGTACCCG AGGC (164) AGGC (145) 575chr11: chr11: TGCAGCTGGCCC TGCAGCTGGCCC 0 14 3.91 1.39E−07 3′ss Mel.64002365-64002911 64002365-64002929 CCGCCCAGGTCT CCGCCCAGGCCCTTTCTCTCCCAC CTGTCTCCCAGC AGGC (638) CTGA (639) 576 chr12: chr12:GCCTGCCTTTGA GCCTGCCTTTGA 0 14 3.91 1.83E−03 3′ss Mel.113346629-113348840 113346629-113348855 TGCCCTGGATTT TGCCCTGGGTCATGCCCGAACAGG GTTGACTGGCGG TCAG (71) CTAT (72) 577 chr17: chr17:CCAAGCTGGTGT CCAAGCTGGTGT 0 14 3.91 1.08E−03 3′ss Mel. 78188582-7818883178188564-78188831 GCGCACAGGCCT GCGCACAGGCAT CTCTTCCCGCCC CATCGGGAAGAAAGGC (73) GCAC (74) 578 chr2: chr2: GTGTGGCAAGTA GTGTGGCAAGTA 0 14 3.911.45E−02 3′ss Mel. 85848702-85850728 85848702-85850768 CTTTCAAGTATCCTTTCAAGGCCG TGCCCTTCTATT GGGTTTGAAGTC ACAG (882) TCAC (883) 579 chr12:chr12: AAAATCATTGAT AAAATCATTGAT 0 13 3.81 1.44E−03 3′ss Mel.29450133-29460566 29450133-29460590 TCCCTTGAAATT TCCCTTGAGTGGCTCTTTACTCTA TTAGACGATGCT CCTT (884) ATTA (885) 580 chr14: chr14:GTGGGGGGCCAT GTGGGGGGCCAT 0 13 3.81 2.75E−04 3′ss Mel. 23237380-2323898523237380-23238999 TGCTGCATTTTG TGCTGCATGTAC TATTTTCCAGGT AGTCTTTGCCCGACAG (122) CTGC (123) 581 chr22: chr22: CGCTGGCACCAT CGCTGGCACCAT 0 133.81 5.09E−08 3′ss Mel. 36627480-36629198 36627512-36629198 GAACCCAGTATTGAACCCAGAGAG TCCAGGACCAAG CAGTATCTTTAT TGAG (199) TGAG (200) 582 chr19:chr19: TGCCTGTGGACA TGCCTGTGGACA 0 12 3.70 4.53E−04 3′ss Mel.14031735-14034130 14031735-14034145 TCACCAAGCCTC TCACCAAGGTGCGTCCTCCCCAGG CGCCTGCCCCTG TGCC (59) TCAA (60) 583 chr20: chr20:TTTGCAGGGAAT TTTGCAGGGAAT 0 12 3.70 9.65E−05 3′ss Mel. 35282126-3528476235282104-35284762 GGGCTACATCCC GGGCTACATACC CTTGGTTCTCTG ATCTGCCAGCATTTAC (35) GACT (36) 584 chr22: chr22: TGCTCAGAGGTG TGCTCAGAGGTG 0 123.70 8.43E−07 3′ss Mel. 19948812-19950181 19948812-19950049 CTTTGAAGCCCACTTTGAAGATGC TCCACAACCTGC CGGAGGCCCCGC TCAT (886) CTCT (887) 585 chr2:chr2: CAAGATAGATAT CAAGATAGATAT 0 12 3.70 3.94E−03 3′ss Mel.170669034-170671986 170669016-170671986 TATAGCAGGTGG TATAGCAGAACTCTTTTGTTTTAC TCGATATGACCT AGAA (99) GCCA (100) 586 chr15: chr15:GCCTCACTGAGC GCCTCACTGAGC 2 37 3.66 8.44E−08 exon Mel. 25207356-2521217525207356-25213078 AACCAAGAGTAG AACCAAGAGTGT incl. TGACTTGTCAGGCAGTTGTACCCG AGGA (144) AGGC (145) 587 chr11: chr11: CCACGGCCACGGCCACGGCCACGG 4 60 3.61 3.80E−03 3′ss Mel. 8704812-87055368704812-8705552 CCGCATAGCTTT CCGCATAGGCAA GTATTCCTGCAG GCACCGGAAGCA GCAA(888) CCCC (889) 588 chr11: chr11: CATGCCGGGGCC CATGCCGGGGCC 0 11 3.581.83E−02 3′ss Mel. 11988666-11989941 11988645-11989941 AGAGGATGGCTCAGAGGATGCTCT TTTCCACCTGTC GCACCCGGGACA TGCA (890) GTGA (891) 589 chr16:chr16: GGCCAAGCAAGA GGCCAAGCAAGA 0 11 3.58 1.88E−02 3′ss Mel.19838459-19843229 19838459-19867808 ACAAAAAGTATT ACAAAAAGTGAATTCTTCTAGGAT ATGCAAAATGGA GGAA (892) GGAC (893) 590 chr1: chr1:GGCTCCCATTCT GGCTCCCATTCT 0 11 3.58 2.42E−03 3′ss Mel.155630724-155631097 155630704-155631097 GGTTAAAGAGTG GGTTAAAGGCCATTCTCATTTCCA GTCTGCCATCCA ATAG (195) TCCA (196) 591 chr1: chr1:GAAGAACAGGAT GAAGAACAGGAT 0 11 3.58 1.74E−02 3′ss Mel.219366593-219383856 219366593-219383873 ATTAATAGTATG ATTAATAGGAGGTTTTTGTTTTTA ATTCTCTATGGG GGAG (894) AGGA (895) 592 chr19: chr19:CAAGCAGGTCCA CAAGCAGGTCCA 0 10 3.46 2.28E−04 3′ss Mel. 5595521-55988035595508-5598803 AAGAGAGATTTT AAGAGAGAAGCT GGTAAACAGAGC CCAAGAGTCAGG TCCA(138) ATCG (139) 593 chr5: chr5: CAATTCAGTAGA AGGTCTTCCTGG 0 10 3.462.42E−02 5′ss Mel. 462644-464404 462422-464404 TTCACCCTCAAC ACCTGGAGCAACATCTGAATGAAT ATCTGAATGAAT TGAT (896) TGAT (897) 594 chr9: chr9:GGGAGATGGATA GGGAGATGGATA 3 41 3.39 1.97E−10 3′ss Mel. 35813153-3581326235813142-35813262 CCGACTTGCTCA CCGACTTGTGAT ATTTCAGTGATC CAACGATGGGAAAACG (146) GCTG (147) 595 chr1: chr1: AGAGGGCACGGG AGAGGGCACGGG 2 293.32 1.42E−03 3′ss Mel. 205240383-205240923 205240383-205240940ACATCCAGCCCC ACATCCAGGAGG TCTGCCCCTGCA CCGTGGAGTCCT GGAG (898) GCCT(899) 596 chr11: chr11: TTCTCCAGGACC TTCTCCAGGACC 0 9 3.32 6.24E−03 3′ssMel. 125442465-125445146 125442465-125445158 TTGCCAGACCTT TTGCCAGAGGAATTCTATAGGGAA TCAAAGACTCCA TCAA (150) TCTG (151) 597 chr11: chr11:GGATGACCGGGA GGATGACCGGGA 0 9 3.32 3.79E−04 3′ss Mel. 71939542-7193969071939542-71939770 TGCCTCAGTCAC TGCCTCAGATGG TTTACAGCTGCA GGAGGATGAGAATCGT (47) GCCC (48) 598 chr16: chr16: AGATGATTGAGG AGATGATTGAGG 0 9 3.321.06E−02 3′ss Mel. 70292147-70292882 70292120-70292882 CAGCCAAGCTCTCAGCCAAGGCCG TTTCTGTCTTCT TCTATACCCAGG TGGT (900) ATTG (901) 599 chr2:chr2: GAGGAGCCACAC GAGGAGCCACAC 0 9 3.32 2.20E−02 3′ss Mel.220044485-220044888 220044485-220044831 TCTGACAGATAC TCTGACAGTGAGCTGGCTGAGAGC GGTGCGGGGTCA TGGC (107) GGCG (108) 600 chr3: chr3:GCTGCTCTCTTC GCTGCTCTCTTC 0 9 3.32 2.87E−06 3′ss Mel. 45043100-4504676745043100-45046782 AATACAAGTGCT AATACAAGGATA TCTGCTTCCAGG CCAAGGGTTCGAATAC (902) GTTT (903) 601 chr9: chr9: AATAGAACTTCC AATAGAACTTCC 7 763.27 4.47E−08 3′ss Mel. 101891382-101894778 101891382-101894790AACTACTGGCCC AACTACTGTAAA TTTTTCAGTAAA GTCATCACCTGG GTCA (904) CCTT(905) 602 chr17: chr17: CTATTTCACTCT CTATTTCACTCT 2 27 3.22 1.02E−053′ss Mel. 7131030-7131295 7131102-7131295 CCCCCGAACCTA CCCCCGAAATGATCCAGGTTCCTC GCCCATCCAGCC CTCC (33) AATT (34) 603 chr17: chr17:TGTTACTGCAGT TGTTACTGCAGT 1 17 3.17 2.33E−03 3′ss Mel. 79556145-7956314179556130-79563141 GGCTACAGGTCT GGCTACAGGTGG CTCTCTTGCAGG TCCTGACAACCATGGT (906) AGTC (907) 604 chr13: chr13: ACATCACAAAGC ACATCACAAAGC 0 83.17 1.95E−03 3′ss Mel. 45841511-45857556 45841511-45857576 AACCTGTGGGGTAACCTGTGGTGT TTTGTTTTTGTT ACCTGAAGGAAA TTAG (908) TCTT (909) 605 chr14:chr14: GGTGCTGGCTGC GGTGCTGGCTGC 0 8 3.17 3.94E−03 3′ss Mel.105176525-105177255 105176525-105177273 CTGCGAAACCCT CTGCGAAAGCCTGGCTGCCCCTGC GCTCACCAGCCG AGGC (910) CCAG (911) 606 chr16: chr16:CACCAAGCAGAG CACCAAGCAGAG 0 8 3.17 7.87E−04 3′ss Mel. 15129410-1512985215129410-15129872 GCTTCCAGTCTG GCTTCCAGGCCA TCTGCCCTTTCT GAAGCCTTTTAAGTAG (216) AAGG (217) 607 chr17: chr17: CCTCTCTGCTCG CCTCTCTGCTCG 0 83.17 7.21E−08 3′ss Mel. 17062316-17064532 17062316-17064553 AGAAGGAGTGTGAGAAGGAGCTGG TGTCTTTTTGCC AGCAGAGCCAGA AACA (912) AGGA (913) 608 chr19:chr19: ATCACAACCGGA ATCACAACCGGA 0 8 3.17 1.45E−02 3′ss Mel.15491444-15507960 15491423-15507960 ACCGCAGGCTCC ACCGCAGGCTCATTCTGCCCTGCC TGATGGAGCAGT CGCA (661) CCAA (662) 609 chr3: chr3:CTGGAAGCTCAA CTGGAAGCTCAA 0 8 3.17 4.68E−04 3′ss Mel.112724877-112727017 112724851-112727017 GGTACTAGATTT GGTACTAGTTTGTTCCTCTCTCTG CCAAAGAAACTA TCTT (914) GAGT (915) 610 chr1: chr1:CCCGAGCTCAGA CCCGAGCTCAGA 4 41 3.07 3.31E−04 3′ss Mel. 3548881-35499613548902-3549961 GAGTAAATTCTC GAGTAAATATGA CTTACAGACACT GATCGCCTCTGT GAAA(177) CCCA (178) 611 chr2: chr2: TATCCATTCCTG TATCCATTCCTG 1 15 3.003.44E−05 3′ss Mel. 178096758-178097119 178096736-178097119 AGTTACAGTATAAGTTACAGTGTC AACTTCCTTCTC TTAATATTGAAA ATGC (156) ATGA (157) 612 chr11:chr11: CGGCGATGACTC CGGCGATGACTC 0 7 3.00 2.48E−02 3′ss Mel.62554999-62556481 62554999-62556494 GGACCCAGCTTC GGACCCAGGGCTTCTCCACAGGGC CCTTCAGTGGTA TCCT (916) GATG (917) 613 chr15: chr15:CCGCCAGGAGAA CCGCCAGGAGAA 0 7 3.00 9.38E−04 3′ss Mel. 41102168-4110227441102168-41102268 CAAGCCCATCCC CAAGCCCAAGTT CTCACAGGCAGA AGTCCCCTCACAGATA (918) GGCA (919) 614 chr16: chr16: CAGCAGCAGCTC CAGCAGCAGCTC 0 73.00 9.09E−03 3′ss Mel. 48311390-48330007 48311390-48329925 TGCTTGAGCTACTGCTTGAGGTGT TGCCAACACCAC TGGATCCTGAAC TGCT (920) AAAA (921) 615 chr2:chr2: AGACAAGGGATT AGACAAGGGATT 0 7 3.00 6.35E−04 3′ss Mel.26437445-26437921 26437430-26437921 GGTGGAAACATT GGTGGAAAAATTTTATTTTACAGA GACAGCGTATGC ATTG (295) CATG (296) 616 chr3: chr3:GCACTTATGGTG GCACTTATGGTG 0 7 3.00 1.74E−07 3′ss Mel. 48638222-4863840748638273-48638407 GTGGCGTGAGTT GTGGCGTGCACC TCCAGACCTTCA TGTCCAGCCCACGCAT (922) TGGC (923) 617 chr19: chr19: GTGCTTGGAGCC GTGCTTGGAGCC 4 352.85 1.91E−07 3′ss Mel. 55776746-55777253 55776757-55777253 CTGTGCAGACTTCTGTGCAGCCTG TCCGCAGGGTGT GTGACAGACTTT GCGC (179) CCGC (180) 618 chr9:chr9: GTGGCTCCAGTA GACCTGCTCAAG 8 63 2.83 2.74E−02 5′ss Mel.119414072-119488049 119414072-119449344 TCAGAAAGAGAC TTCACTCAAGACCACAGAGCTGGG CACAGAGCTGGG CAGC (924) CAGC (925) 619 chr10: chr10:TGTGGGCATGGA TGTGGGCATGGA 0 6 2.81 8.27E−08 3′ss Mel. 82264534-8226695482264534-82266983 GCGAAAAGTGCT GCGAAAAGGGTG GCCCTGCTTTCT TGCTGTCCGACCCTGT (926) TCAC (927) 620 chr12: chr12: TTCCTCTTCCCC TTCCTCTTCCCC 0 62.81 4.32E−06 3′ss Mel. 56361953-56362539 56361953-56362561 TCATCAAGTCCTTCATCAAGAGCT CTCTTTCTCCTT ATCTGTTCCAGC TGTC (928) TGCT (929) 621 chr19:chr19: GGGGCACTGACA GGGGCACTGACA 0 6 2.81 2.67E−02 3′ss Mel.50149459-50149761 50149459-50149782 CGGCTACTAGCC CGGCTACTGTGTTCTCTGGCCTCT TGGACATGGCCA TCCA (930) CGGA (931) 622 chr20: chr20:ACATGAAGGTGG ACATGAAGGTGG 0 6 2.81 1.25E−04 3′ss Mel. 34144042-3414476134144042-34144743 ACGGAGAGTTCT ACGGAGAGGTAC CTGTGACCAGAC TGAGGACAAATCATGA (250) AGTT (50) 623 chrX: chrX: TGACTCCGCTGC TGACTCCGCTGC 0 6 2.811.80E−02 3′ss Mel. 118923962-118925536 118923974-118925536 TCGCCATGACTTTCGCCATGTCTT TCAGGATTAAGC CTCACAAGACTT GATT (697) TCAG (698) 624 chr2:chr2: CCCCTGAGATGA CCCCTGAGATGA 3 25 2.70 6.46E−06 exon Mel.27260570-27260682 27260570-27261013 AGAAAGAGCTCC AGAAAGAGCTCC incl.CTGTTGACAGCT TGAGCAGCCTGA GCCT (183) CTGA (184) 625 chr2: chr2:AGGCTGTAGCAG AGGCTGTAGCAG 1 12 2.70 2.24E−02 3′ss Mel. 99225189-9922610599225189-99226218 GACTCCAGGGTT GACTCCAGGAAG GGGAAGAACATG ATGTTACCGAGTGAAA (932) ACTT (933) 626 chr8: chr8: CCGAGGATGCTA CCGAGGATGCTA 4 302.63 6.42E−03 3′ss Mel. 133811106-133811328 133811106-133816063AGGGGCAGTTTC AGGGGCAGGATT TGTTCCAGGTGA GGATAGCTTTAG AATC (934) TCAA(935) 627 chr21: chr21: GCCTCCCGGTCC GCCTCCCGGTCC 4 29 2.58 9.60E−043′ss Mel. 46935066-46945730 46936054-46945730 GCAAGCAGAATG GCAAGCAGTTCCAAGAACTGCATG AGTTATACTCCG TGGC (936) TGTA (937) 628 chr17: chr17:TCGTAACAGGGG CTGTGACGGGTG 3 23 2.58 1.22E−02 exon Mel. 27210249-2721287427210249-27211242 TTGCACAGGTGA TCGCCCAGGTGA skip AGATCATGACGGAGATCATGACGG AGAA (938) AGAA (939) 629 chr6: chr6: GTTTGGGGAAGTGTTTGGGGAAGT 1 11 2.58 2.07E−05 exon Mel. 112020873-112021306112017659-112021306 ATGGATGGAGAA ATGGATGGGTAC incl. AGCTGATGGTTTCTGGAATGGAAA GTGT (940) CACA (941) 630 chr6: chr6: TAACTAATCCTTCAGCCTACCAGA 1 11 2.58 4.06E−02 5′ss Mel. 39854223-3985526139851845-39855261 CTCAGCAGAAAG GGCACCAGAAAG AGCTGGGCTCCA AGCTGGGCTCCACTGA (942) CTGA (943) 631 chr11: chr11: AGTCCAGCCCCA AGTCCAGCCCCA 0 52.58 9.35E−03 3′ss Mel. 64900740-64900940 64900723-64900940 GCATGGCACCTCGCATGGCAGTCC TCCCCACTCCTA TGTACATCCAGG GGTC (136) CCTT (137) 632 chr16:chr16: GGATCCTTCACC GGATCCTTCACC 0 5 2.58 1.87E−03 3′ss Mel.1402307-1411686 1402307-1411743 CGTGTCTGTCTT CGTGTCTGGACC TGCAGACAGGTTCGTGCATCTCTT CTGT (85) CCGA (86) 633 chr17: chr17: GCATCTCAGCCCGCATCTCAGCCC 0 5 2.58 1.16E−05 3′ss Mel. 16344444-1634467016344444-16344681 AAGAGAAGTTTC AAGAGAAGGTTA TTTGCAGGTTAT TATTCCCAGAGGATTC (287) ATGT (288) 634 chr1: chr1: CTACACAGAGCT CTACACAGAGCT 0 5 2.582.48E−06 3′ss Mel. 32096333-32098095 32096443-32098095 GCAGCAAGGTGTGCAGCAAGCTCT GCACCCAGCTGC GTCCCAAATGGG AGGT (291) CTAC (292) 635 chr22:chr22: CCTGCGCAACTG CCTGCGCAACTG 0 5 2.58 1.56E−04 3′ss Mel.19164146-19164358 19164206-19164358 GTACCGAGGCGC GTACCGAGGGGAAGCCAGTGTCTT CAACCCCAACAA TGGA (944) GCCC (945) 636 chr3: chr3:ATAAAAATTGCT ATAAAAATTGCT 0 5 2.58 2.28E−03 3′ss Mel.131181737-131186934 131181719-131186934 TAGTAAAGATTT TAGTAAAGGTCATTGCCTTCTCTC AAGATTCTAAAC AGGT (946) TGCC (947) 637 chr8: chr8:TGAGTTCATGGA TGAGTTCATGGA 0 5 2.58 3.48E−02 3′ss Mel. 98817692-9882753198817692-98827555 TGATGCCAAAAT TGATGCCAACAT TCTTTTTAATCT GTGCATTGCCATTTCG (948) TGCG (949) 638 chrX: chrX: AGAGTTGAAAAA AGAGTTGAAAAA 0 5 2.584.97E−03 3′ss Mel. 24091380-24092454 24091380-24094838 CACTGGCGTCTCCACTGGCGTTTA CTTTTCAGGAAT ATTGGTTGGGGT CACA (950) CAGA (951) 639 chr12:chr12: GGCCAGCCCCCT GGCCAGCCCCCT 8 51 2.53 3.07E−09 3′ss Mel.120934019-120934204 120934019-120934218 TCTCCACGGCCT TCTCCACGGTAATGCCCACTAGGT CCATGTGCGACC AACC (206) GAAA (207) 640 chr9: chr9:CACCACGCCGAG CACCACGCCGAG 3 21 2.46 2.87E−02 3′ss Mel.125023777-125026993 125023787-125026993 GCCACGAGACAT GCCACGAGTATTTGATGGAAGCAG TCATAGACATTG AAAC (142) ATGG (143) 641 chr10: chr10:TGGGGCCACAAA TGGGGCCACAAA 4 24 2.32 1.77E−02 exon Mel. 74994698-7499906974994698-74994950 GACAGATGCTGG GACAGATGAAAC skip ATACACAGTATCCCCATGGCGACT GTCG (952) CTAG (953) 642 chr1: chr1: CTTGCCTTCCCACTTGCCTTCCCA 1 9 2.32 1.49E−04 3′ss Mel. 154246074-154246225154246074-154246249 TCCTCCTGCAAA TCCTCCTGAACT CACCTGCCACCT TCCAGGTCCTGATTCT (289) GTCA (290) 643 chr11: chr11: GGGGACAGTGAA GGGGACAGTGAA 0 42.32 1.19E−05 3′ss Mel. 57100545-57100908 57100623-57100908 ATTTGGTGGCAAATTTGGTGGGCA GAATGAGGTGAC GCTGCTTTCCTT ACTG (103) TGAC (104) 644 chr16:chr16: GAACTGGCACCG GAACTGGCACCG 0 4 2.32 1.03E−03 3′ss Mel.313774-313996 313774-314014 ACAGACAGTGTC ACAGACAGATCC CCCTCCCTCCCCTGTTTCTGGACC AGAT (244) TTGG (245) 645 chr17: chr17: AACATGGAATCAAACATGGAATCA 0 4 2.32 1.03E−03 3′ss Mel. 34147441-3414962534147441-34149643 TCAGGAAGTTCT TCAGGAAGCCAA CCATTTCTATTT GGTGGAAGAGCAAGCC (954) CCTT (955) 646 chr1: chr1: CGTGCGTGTGTG CTTAGGAAAGAC 0 4 2.322.87E−02 5′ss Mel. 1480382-1497319 1480382-1500152 TGCTCTTGCTATAAAGAACTCTAT ACACAGAATGGG ACACAGAATGGG ATTT (956) ATTT (957) 647 chr22:chr22: CCCAGCCTGCTG CCCAGCCTGCTG 0 4 2.32 3.33E−02 3′ss Mel.24108483-24109560 24108462-24109560 TCCAGCAGCCTC TCCAGCAGGCCCTTGCACTGTACC CCACCCCCGCTG CCCA (958) CCCC (959) 648 chr22: chr22:ACCCAAGGCTCG ACCCAAGGCTCG 0 4 2.32 5.75E−03 3′ss Mel. 44559810-4456446044559810-44564481 TCCTGAAGTTTC TCCTGAAGACGT TCTGTTTCCTTC GGTTAACTTGGATGCA (960) CCTC (961) 649 chr5: chr5: AGATTGAAGCTA AGATTGAAGCTA 0 4 2.321.38E−03 3′ss Mel. 132439718-132439902 132439718-132439924 AAATTAAGTTTTAAATTAAGGAGC CTGTCTTACCCA TGACAAGTACTT TTCC (348) GTAG (349) 650 chr5:chr5: GAACCCGGTGGT GAACCCGGTGGT 0 4 2.32 5.33E−04 3′ss Mel.175815974-175816311 175815974-175816331 ACCCATAGTTGC ACCCATAGGTTGTTTGTCCCCTCC CCTGGCCACGGC TCAG (962) GGCC (963) 651 chr7: chr7:AATGGAAGTACC AATGGAAGTACC 0 4 2.32 7.50E−03 3′ss Mel. 74131270-7413317974131270-74133197 AGCAGAAGAATT AGCAGAAGATTC TTATTTTTTTCA TACTCAACATGTAGAT (964) CCCT (965) 652 chr20: chr20: GGCAGCTGTTAG GGCAGCTGTTAG 7 372.25 4.91E−02 exon Mel. 57227143-57234678 57227143-57242545 CCGAGCAAGAGCCCGAGCAACTTG incl. TGGACGAGGTAT CTGATGACCGTA TGTG (966) TGGC (967) 653chr16: chr16: GAGATTCTGAAG GAGATTCTGAAG 3 18 2.25 1.03E−03 3′ss Mel.54954250-54957496 54954322-54957496 ATAAGGAGTTCT ATAAGGAGGTAACTTGTAGGATGC AACCTGTTTAGA CACT (313) AATT (314) 654 chrX: chrX:AAAAGAAACTGA AAAAGAAACTGA 14 70 2.24 5.98E−06 3′ss Mel.129771378-129790554 129771384-129790554 GGAATCAGTATC GGAATCAGCCTTACAGGCAGAAGC AGTATCACAGGC TCTG (303) AGAA (304) 655 chr13: chr13:GTTTAGAAATGG GTTTAGAAATGG 18 88 2.23 1.12E−04 3′ss Mel.45911538-45912794 45911523-45912794 AAAAATGTTTTT AAAAATGTTAACTGCTTTTACAGT AAATGTGGCAAT AACA (968) TATT (969) 656 chr2: chr2:CCAAGAGACAGC CCCCTGAGATGA 5 27 2.22 4.64E−05 exon Mel. 27260760-2726101327260570-27261013 ACATTCAGCTCC AGAAAGAGCTCC incl. TGAGCAGCCTGATGAGCAGCCTGA CTGA (315) CTGA (184) 657 chr1: chr1: TTGGAAGCGAATTTGGAAGCGAAT 1 8 2.17 6.85E−03 3′ss Mel. 23398690-2339976623398690-23399784 CCCCCAAGTCCT CCCCCAAGTGAT TTGTTCTTTTGC GTATATCTCTCAAGTG (210) TCAA (211) 658 chr6: chr6: AGGATGTGGCTG AGGATGTGGCTG 1 8 2.172.70E−05 3′ss Mel. 31602334-31602574 31602334-31602529 GCACAGAAGTGTGCACAGAAATGA CATCAGGTCCCT GTCAGTCTGACA GCAG (148) GTGG (149) 659 chr3:chr3: AAATCTCGTGGA AAATCTCGTGGA 7 33 2.09 4.05E−02 3′ss Mel.16310782-16312435 16310782-16312451 CTTCTAAGTTTT CTTCTAAGAAAGCTGTTTGCCCAG CGCCATGGCCTG AAAG (970) TGCT (971) 660 chr11: chr11:AGTTCCGGGGCT AGTTCCGGGGCT 0 3 2.00 2.75E−02 3′ss Mel. 68838888-6883937568838888-68839390 ACCTGATGCCTT ACCTGATGAAAT CCTCTTTGCAGA CTCTCCAGACCTAATC (972) CGCT (973) 661 chr12: chr12: GGCACCCCAAAA GGCACCCCAAAA 0 32.00 1.12E−02 3′ss Mel. 58109976-58110164 58109976-58110194 GATGGCAGATCAGATGGCAGGTGC GTCTCTCCCTGT GAGCCCGACCAA TCTC (285) GGAT (286) 662 chr1:chr1: AAGAAGGAATCC AAGAAGGAATCC 0 3 2.00 7.34E−03 3′ss Mel.32377442-32381495 32377427-32381495 ACGTTCTAGTCA ACGTTCTAGATTTTTCTTTTCAGG GGCCATTTGATG ATTG (974) ATGG (975) 663 chr22: chr22:CGCTGGCACCAT CGCTGGCACCAT 0 3 2.00 2.55E−02 3′ss Mel. 36627471-3662919836627512-36629198 GAACCCAGGACC GAACCCAGAGAG AAGTGAGCAGAG CAGTATCTTTATAGAA (976) TGAG (200) 664 chr3: chr3: GCAACCAGTTTG GCAACCAGTTTG 0 3 2.003.20E−03 3′ss Mel. 49395199-49395459 49395180-49395459 GGCATCAGCTGCGGCATCAGGAGA CCTTCTCTCCTG ACGCCAAGAACG TAGG (342) AAGA (343) 665 chr6:chr6: AGCCCCTGCTTG AGCCCCTGCTTG 0 3 2.00 4.68E−04 3′ss Mel.170844509-170846321 170844493-170846321 ACAACCAGTTTC ACAACCAGGTTGATGTCCCACCAG GTTTTAAGAACA GTTG (977) TGCA (978) 666 chr9: chr9:CCAAGGACTGCA CCAAGGACTGCA 0 3 2.00 4.46E−02 3′ss Mel.139837449-139837800 139837395-139837800 CTGTGAAGGCCC CTGTGAAGATCTCCGCCCCGCGAC GGAGCAACGACC CTGG (175) TGAC (176) 667 chr10: chr10:TTGGCTGTAGGA TTGGCTGTAGGA 8 34 1.96 2.70E−05 exon Mel.103904064-103908128 103904064-103904776 AACTCAGGGTCC AACTCAGGCGGC skipAGCTGTAGTTCC GTTGACATTCCC TCTG (979) CAGG (980) 668 chr17: chr17:TGTATCTCCGAC TGTATCTCCGAC 6 26 1.95 3.79E−02 exon Mel. 27212965-2721596227211333-27215962 ACTCAGAGACTG ACTCAGAGGATT incl. TCTCTGGAGGTTTCCCTAGAGATT ATGA (981) ATGA (982) 669 chrX: chrX: AGGCTGATCTACAGGCTGATCTAC 2 10 1.87 5.30E−03 3′ss Mel. 15849691-1586350115845495-15863501 TGCAGGAGCCAC TGCAGGAGGAAG GTCATGAATATT CTGAAACCCCACTTAA (983) GTAG (984) 670 chr2: chr2: GGAAATGGGACA GGAAATGGGACA 14 521.82 4.43E−06 3′ss Mel. 230657846-230659894 230657861-230659894GGAGGCAGAGGA GGAGGCAGCTTT TCACAGGCTTTA TCTCTCAACAGA AAAT (387) GGAT(388) 671 chr5: chr5: GCTCAGCCCCCT TGACCCTGCAGC 5 20 1.81 2.74E−03 exonMel. 141694720-141699308 141694720-141704408 CCCCACAGGGCC TCCTCAAAGGCCincl. CCTAGAAGCCTG CCTAGAAGCCTG TTTC (985) TTTC (986) 672 chr19: chr19:GCCGACCCGCCT GCCGACCCGCCT 3 13 1.81 4.16E−03 3′ss Mel. 3542975-35448063544730-3544806 GCGACGCTCTTT GCGACGCTGGGA TCTTGCCTGGAG CCGTGATGCCCG AAGA(987) GCCC (988) 673 chr3: chr3: TGCGGAGACCCC TGCGGAGACCCC 1 6 1.812.67E−02 exon Mel. 58417711-58419494 58419411-58419494 TTCGGGAGGTGATTCGGGAGGTCT skip CAGTTCGTGATG CCGGGCTGCTGA CTAT (989) AGAG (990) 674chr6: chr6: CTATCAGTAGGT GCATTGATGTGG 1 6 1.81 2.71E−03 exon Mel.108370622-108370735 108370622-108372234 TTTTAGAGATGA AAGATGCAATGA incl.ACATCACTCGAA ACATCACTCGAA AACT (991) AACT (992) 675 chr6: chr6:GCATTGATGTGG GCATTGATGTGG 1 6 1.81 1.84E−03 exon Mel.108370787-108372234 108370622-108372234 AAGATGCAGTTT AAGATGCAATGA incl.TTTTCCTGGCAG ACATCACTCGAA AAGA (993) AACT (992) 676 chr6: chr6:CAGTGGGCGGAT CAGTGGGCGGAT 1 6 1.81 1.04E−02 3′ss Mel.166779550-166780282 166779594-166780282 GACATTTGGTAC GACATTTGCCCTAGCCTCGGAACT CTGTTGCTATTC GGCT (994) TTTG (995) 677 chr7: chr7:GGTGTCCATGGC GGTGTCCATGGC 1 6 1.81 4.73E−02 exon Mel.128033792-128034331 128033082-128034331 CTGCACTCCTAT CTGCACTCTTAC incl.ACCTTTCTGCCG GAAAAGCGGCTG TGTA (996) TACT (997) 678 chr6: chr6:ACTGGGAAGTTC ACTGGGAAGTTC 10 37 1.79 1.30E−02 exon Mel.136597127-136599002 136597646-136599002 TTAAAAAGTCCC TTAAAAAGGTTC skipCCTCTACACAAG ACAGATGAAGAG AATC (998) TCTA (999) 679 chr16: chr16:GAGATTCTGAAG GAGATTCTGAAG 20 69 1.74 1.28E−05 3′ss Mel.54954239-54957496 54954322-54957496 ATAAGGAGGATG ATAAGGAGGTAACCACTGGAAATG AACCTGTTTAGA TTGA (322) AATT (314) 680 chr4: chr4:GCTGAGCGGGGC TCCAACAAGCAC 20 69 1.74 4.13E−05 exon Mel.17806394-17812069 17806394-17806729 GACCCGAGTCTT CTCTGAAGTCTT skipCTCATTCACAGG CTCATTCACAGG TTAA (1000) TTAA (832) 681 chr19: chr19:AGTGGCAGTGGC AGTGGCAGTGGC 8 29 1.74 8.03E−04 3′ss Mel. 6731065-67312096731122-6731209 TGTACCAGCCCA TGTACCAGCTCT CAGGAAACAACC TGGTGGAGGGCT CGTA(311) CCAC (312) 682 chr16: chr16: TGTTCCACCTCC TGTTCCACCTCC 6 22 1.722.96E−02 3′ss Mel. 28842393-28843507 28842393-28843525 TCCTGCAGCTCCTCCTGCAGTGGG CCCTTTTCTTCC CCGGATGTATCC AGTG (1001) CCCG (1002) 683 chr3:chr3: ACCCATGAGAAT CTGGCCCCTGAG 8 28 1.69 8.95E−03 exon Mel.50615004-50617274 50616357-50617274 GCTCAGAGCTAT ATCCGCAGCTAT skipGAAGACCCCGCG GAAGACCCCGCG GCCC (1003) GCCC (1004) 684 chr11: chr11:CAAGCTCGAGTC CAAGCTCGAGTC 4 15 1.68 8.31E−03 exon Mel. 772521-774007773629-774007 CATCGATGAACC CATCGATGGTGC skip CATCTGCGCCGT CCGGTACCATGCCGGC (1005) CCTC (1006) 685 chr2: chr2: CTTCACTGTCAC CTTCACTGTCAC 9 301.63 2.25E−02 3′ss Mel. 220424219-220427123 220426730-220427123CGTCACAGAACC CGTCACAGAGTC CCCAGTGCGGAT TTACCAAAGTCA CATA (1007) GGAC(1008) 686 chr3: chr3: GTCTTCCAATGG GTCTTCCAATGG 10 33 1.63 1.04E−023′ss Mel. 148759467-148759952 148759455-148759952 CCCCTCAGCCTTCCCCTCAGGAAA TTCTCTAGGAAA TGATACACCTGA TGAT (234) AGAA (235) 687 chr5:chr5: AGAAACAGAAAC AGAAACAGAAAC 5 17 1.58 1.55E−02 exon Mel.34945908-34949647 34945908-34950274 CAGCACAGGATG CAGCACAGAATT incl.TACCTGGCAAAG ATGATGACAATT ATTC (1009) TCAA (1010) 688 chr6: chr6:TTCTGCATCTGT AAAGGAGTGCTT 2 8 1.58 1.45E−02 exon Mel.158589427-158613008 158591570-158613008 GGGCCGAGTGAT ATAGAATGTGAT skipCCTGCCATGAAG CCTGCCATGAAG CAGT (1011) CAGT (1012) 689 chr14: chr14:AGGATCGGCAAC CTGGGATAAGAG 1 5 1.58 1.98E−02 exon Mel. 23495584-2349695323495584-23502576 ATGGCAAGGCCT AGGCCCTGGCCT incl. CTACTACGTGGACTACTACGTGGA CAGT (1013) CAGT (1014) 690 chr6: chr6: GTTCAGGACACAGGGAGGGAGAGA 1 5 1.58 1.23E−02 exon Mel. 33669197-3367847133669197-33679325 ATAAGCAGGTTG ATACCCAGGTTG incl. CAGAGCCTGAGGCAGAGCCTGAGG CCTG (1015) CCTG (1016) 691 chr10: chr10: TACCCGGATGATTACCCGGATGAT 0 2 1.58 2.58E−04 3′ss Mel. 102286851-102289136102286831-102289136 GGCATGGGAAGT GGCATGGGGTAT TCTTGCTGTCTT GGCGACTACCCGTCAG (1017) AAGC (1018) 692 chr11: chr11: GACATATGAGTC GACATATGAGTC 0 21.58 2.45E−02 3′ss Mel. 66333872-66334716 66333875-66334716 AAAGGAAGCCCGAAAGGAAGAAGC GTGGCGCCTGTC CCGGTGGCGCCT CGTC (1019) GTCC (1020) 693chr11: chr11: CGGATCAACTTC CGGATCAACTTC 0 2 1.58 2.65E−03 3′ss Mel.8705628-8706243 8705628-8706264 GACAAATAGTGG GACAAATACCAC TTGTTACCTCTTCCAGGCTACTTT CCTA (1021) GGGA (1022) 694 chr12: chr12: TTATAGGCGTGATTATAGGCGTGA 0 2 1.58 1.03E−03 3′ss Mel. 53421972-5342757453421972-53427589 TGATAGAGTTTC TGATAGAGGTCC ATTTAACTTAGG CCCCCAAAGACCTCCC (1023) CAAA (1024) 695 chr15: chr15: TGGAAATATTTC GCCTCACTGAGC 0 21.58 7.87E−03 exon Mel. 25212387-25213078 25207356-25213078 TAGACTTGGTGTAACCAAGAGTGT incl. CAGTTGTACCCG CAGTTGTACCCG AGGC (1025) AGGC (145) 696chr1: chr1: TCGGCCCAGAAG CTTAGGAAAGAC 0 2 1.58 4.66E−02 5′ss Mel.1480382-1497338 1480382-1500152 AACCCCGCCTAT AAAGAACTCTAT ACACAGAATGGGACACAGAATGGG ATTT (1026) ATTT (957) 697 chr5: chr5: TCTATATCCCCTTCTATATCCCCT 0 2 1.58 1.26E−04 3′ss Mel. 177576859-177577888177576839-177577888 CTAAGACGCACT CTAAGACGGACC TCTTTCCCCTCT TGGGTGCAGCCGGTAG (299) CAGG (300) 698 chr6: chr6: GCTGAAGGGAAA GCTGAAGGGAAA 0 2 1.584.68E−02 3′ss Mel. 42905945-42911535 42905945-42906305 AGACACCAAAACAGACACCAGTTG ACAAACAGCAGA CCTGGCAGAGCA ATGG (1027) GTGG (1028) 699chr17: chr17: CATCATCAAGTT CATCATCAAGTT 5 16 1.50 1.74E−04 intron Mel.2282497-2282499 2282497-2282725 TTTCAATGACGA TTTCAATGAACG reten-GCTGGTCCAGCC TGCTGAGCATCA tion ATCC (1029) CGAT (1030) 700 chr8: chr8:GAGGGCCTGCTC ACATGCTTCAAA 23 66 1.48 1.49E−03 exon Mel.74601048-74621266 74601048-74650518 ATTCAAAGATGT TAAATCAGATGT incl.TCTCAGTGCAGC TCTCAGTGCAGC TGAG (1031) TGAG (1032) 701 chr10: chr10:CTGAGGCTAATG CTGAGGCTAATG 14 40 1.45 2.13E−02 3′ss Mel.35495979-35500583 35495979-35500181 AAAAACAGGGAA AAAAACAGGGAAGCTGCCAAAGAA GCTGCCCGGGAG TGTC (1033) TGTC (1034) 702 chr3: chr3:CGGCTGGGACTC CGGCTGGGACTC 12 34 1.43 1.81E−02 3′ss Mel.119180951-119182182 119180995-119182182 TTCCATGCGTGG TTCCATGCAGTTCACTGGAAGCAG GAAACTGGTTGA ACTG (1035) CAAC (1036) 703 chr4: chr4:AGTGAATGTAGT AGTGAATGTAGT 17 47 1.42 2.45E−02 exon Mel.169919436-169923221 169911479-169923221 TGCACCAGTGAC TGCACCAGGATT incl.AATACTTGTATG TGTACACACAGA GAGT (1037) TATG (1038) 704 chr17: chr17:ATTCACACAGAG TGAGGATCAATC 2 7 1.42 1.30E−02 exon Mel. 55074416-5507821555075859-55078215 CCACCTAGGCCA CTGGGGAGGCCA skip GGCTACCAACGTGGCTACCAACGT CTTT (1039) CTTT (1040) 705 chrX: chrX: AGAAACCTTGAAAGAAACCTTGAA 7 20 1.39 3.40E−02 exon Mel. 2310515-23267852209644-2326785 CGACAAAGAGAC CGACAAAGTGGA incl. GTGAGTCTTGCTATTTTTATACTG GTGT (496) TGAC (495) 706 chrY: chrY: AGAAACCTTGAAAGAAACCTTGAA 7 20 1.39 3.40E−02 exon Mel. 2260515-22767852159644-2276785 CGACAAAGAGAC CGACAAAGTGGA incl. GTGAGTCTTGCTATTTTTATACTG GTGT (496) TGAC (495) 707 chr5: chr5: TGGAAAAGTATATGGAAAAGTATA 4 12 1.38 2.71E−02 exon Mel. 54456224-5445988254456224-54456821 AAGGCAAAATTC AAGGCAAAGTTT skip TTCAAAGAAGGACACTAGTTGTAA ACCA (1041) ACGT (1042) 708 chr15: chr15: ATACTAAGAACAATACTAAGAACA 19 50 1.35 2.54E−02 exon Mel. 76146828-7616129176146828-76152218 ACAATTTGAATG ACAATTTGCTTC skip GGACAACAGAAGGTCAGCAATTGA AAGT (1043) AGTG (1044) 709 chr8: chr8: TGGCCTTGACCTTGGCCTTGACCT 7 19 1.32 3.77E−02 3′ss Mel. 38270113-3827143538271322-38271435 CCAACCAGGTCC CCAACCAGGAGT TGCACCCAGACC ACCTGGACCTGTTCAC (1045) CCAT (1046) 710 chr1: chr1: GAAGGCAGCTGA GAAGGCAGCTGA 3 91.32 1.42E−02 3′ss Mel. 11131045-11132143 11131030-11132143 GCAAACAGTTCTGCAAACAGCTGC CTCCCTTGCAGC CCGGGAACAGGC TGCC (393) AAAG (394) 711 chr11:chr11: TCCTTGAACACT TCCTTGAACACT 1 4 1.32 2.52E−02 exon Mel.62556898-62557357 62556898-62557072 ACAATTAGACCT ACAATTAGCTGT skipCTTCTTGGGTGA TCTGAAGCCCAG ATTT (1047) AAAA (1048) 712 chr14: chr14:ACACCATTGAGG ACACCATTGAGG 1 4 1.32 1.92E−02 exon Mel. 69349309-6935088469349772-69350884 AGATCCAGGTGC AGATCCAGGGAC skip GGCAGCTGGTGCTGACCACAGCCC CTCG (1049) ATGA (1050) 713 chr1: chr1: CCCATGTATAAGCCCATGTATAAG 1 4 1.32 2.77E−02 3′ss Mel. 155227125-155227288155227177-155227288 GCTTTCCGGATG GCTTTCCGGAGT TGCTCTTTGTCC GACAGTTCATTCTCCA (1051) AATT (1052) 714 chr20: chr20: CTCCCAGTGCTG GAGCTGCCACGG 1 41.32 2.02E−02 exon Mel. 25281520-25281967 25281520-25282854 TATATCCCGGAAATACTGAGGGAA incl. .TTCCTGGGGAAG TTCCTGGGGAAG TCGG (1053) TCGG (1054)715 chr7: chr7: GGATGCGCGTCT AGCCGCAGAGCA 1 4 1.32 4.91E−02 exon Mel.142962185-142964709 142962389-142964709 GGTCAAGGGCTG TCCTGGCGGCTG skipCAGAGAAGGCTG CAGAGAAGGCTG GTAT (1055) GTAT (1056) 716 chr8: chr8:ACATGCTTCAAA ACATGCTTCAAA 24 61 1.31 1.74E−02 exon Mel.74621397-74650518 74601048-74650518 TAAATCAGCTTC TAAATCAGATGT incl.TCTCCAAGATAA TCTCAGTGCAGC AATG (1057) TGAG (1032) 717 chr15: chr15:AACAAAGAAATA CTGAGTCTTTAT 16 41 1.30 1.66E−03 exon Mel.49309825-49319561 49309825-49311614 ATTCACAGGATG ATTTTGAGGATG skipAAGATGGGTTTC AAGATGGGTTTC AAGA (1058) AAGA (1059) 718 chrX: chrX:TAGCCACCACTG GGGAAAAGTCTT 11 28 1.27 1.07E−02 exon Mel.148582568-148583604 148582568-148584841 TGTGCCAGGGAT TCACCCTGGGAT incl.ATCTTCTAACCA ATCTTCTAACCA TACC (1060) TACC (1061) 719 chr12: chr12:CCTACCAGCCAC CCTACCAGCCAC 4 11 1.26 2.42E−02 3′ss Mel. 49918679-4991986049918679-49919726 TTCGGGAGGTAT TTCGGGAGGTAT CAGAGTGCTCCA TGCCAGGGAACATCTC (1062) GACG (1063) 720 chr1: chr1: GTCCCGGCTTCC GTCCCGGCTTCC 4 111.26 2.67E−02 exon Mel. 46654652-46655129 46655029-46655129 CCCTACTCGCCTCCCTACTCAGTG skip GGCTCAGAATCT AAGAAGCCACCC AACC (1064) TCAG (1065) 721chr3: chr3: CTTAAGCATATA CTTAAGCATATA 28 68 1.25 2.24E−02 exon Mel.105397415-105400567 105400454-105400567 TTTAAAGGGTGA TTTAAAGGGAGA skipAGATGCTTTTGA TGTTTTTGATTC TGCC (1066) AGCC (1067) 722 chr3: chr3:CAGGAACAAGTA CAGGAACAAGTA 2 6 1.22 4.97E−02 exon Mel. 10023431-1002819010019130-10028190 TCTGACAGAAAA TCTGACAGTCAA incl. TATCTTTCAGGCGTCCTAATTCGA CTGG (1068) AGCA (1069) 723 chr4: chr4: GAAGTTCTGAGGGAAGTTCTGAGG 2 6 1.22 1.07E−02 3′ss Mel. 88898249-8890154488898249-88901197 AAAAGCAGAATG AAAAGCAGCTTT CTGTGTCCTCTG ACAACAAATACCAAGA (1070) CAGA (1071) 724 chr7: chr7: ATCTCCCTCTTG ATCTCCCTCTTG 2 61.22 1.94E−03 3′ss Mel. 23313233-23313672 23313233-23313683 GTGTACAAATTGGTGTACAAAAAA TTTTCAGAAAAC CACAAGGAATAC ACAA (1072) AACC (1073) 725 chr1:chr1: TGCGAGTACTGC TGCGAGTACTGC 6 15 1.19 3.00E−03 exon Mel.214454770-214488104 214454770-214478529 TTCACCAGAAAG TTCACCAGGAAA skipAAGATTGGCCCA GAAGGATTGTCC TGCA (1074) AAAT (1075) 726 chr15: chr15:TCCAGAAAGTGA TCCAGAAAGTGA 15 35 1.17 2.02E−04 exon Mel.101826006-101827112 101826498-101827112 AACTAAAATTTT AACTAAAAGAGC skipAATCCAGGTGCT GTCAGGAAGCAG GGTT (1076) AGAA (1077) 727 chr15: chr15:ACTCAGATGCCG ACTCAGATGCCG 39 88 1.15 2.54E−04 3′ss Mel.74326871-74327483 74326871-74327512 AAAACTCGCCCT AAAACTCGTGCACAGTCTGAGGTT TGGAGCCCATGG CTGT (748) AGAC (749) 728 chrX: chrX:AGATTCTACAGA AGATTCTACAGA 17 39 1.15 2.23E−02 exon Mel.15706981-15720904 15706981-15711085 TAAATCAGATTT TAAATCAGCTGC skipCGGAAACTTCTG ACTTAGTGCATT GCAG (1078) GGAA (1079) 729 chr3: chr3:TGGCTGGCTTCA TGGCTGGCTTCA 40 90 1.15 1.67E−02 exon Mel.183703166-183705557 183700795-183705557 GTGGACCAAATT GTGGACCAGCCT incl.TTCAGGATGGCT TCATGGTGAAAC GTAT (1080) ACCT (1081) 730 chr16: chr16:CCCTGCTCATCA CCCTGCTCATCA 19 40 1.04 9.38E−04 exon Mel. 684797-685280684956-685280 CCTACGGGGAAC CCTACGGGCCCT skip CCAGAATGGGGG ATGCCATCAATGCTTC (1082) GGAA (194) 731 chrX: chrX: CAAACACCTCTT CAAACACCTCTT 11 231.00 2.44E−04 exon Mel. 123224614-123224703 123224614-123227867GATTATAACACG GATTATAATCGG incl. CAGGTAACATGG CGTGGCACAAGC ATGT (468)CTAA (457) 732 chr20: chr20: GGCAGCCACCAC TGATAATTGGGC 10 21 1.002.87E−02 exon Mel. 48700791-48729643 48700791-48713208 GGGCTCGGACAACTCCAAGAACAA skip TTTATGAAAACC TTTATGAAAACC GAAT (1083) GAAT (1084) 733chr19: chr19: ACCGCCCTGCAC ACCGCCCTGCAC 7 15 1.00 2.95E−02 3′ss Mel.617870-618487 617849-618487 TGCTACAGGAGT TGCTACAGGAAG CCTCCGCTCTGCGGCCTGACCTTC CACA (1085) GTCT (1086) 734 chr1: chr1: TCACAATTATAGGTGCTATTAAAG 7 15 1.00 1.48E−02 exon Mel. 220242774-220247308220242774-220246191 GGGAAGAGCTCG AAGAAGATCTCG skip TGGTCTGGGTTGTGGTCTGGGTTG ATCC (1087) ATCC (1088) 735 chr1: chr1: CTCGTCTATGATCTCGTCTATGAT 6 13 1.00 3.26E−02 3′ss Mel. 229431657-229433266229431657-229433228 ATCACCAGATGC ATCACCAGCCGA CCGAATGCTAGC GAAACCTACAATGAGC (1089) GCGC (1090) 736 chr11: chr11: CAATGCCACAGG CAATGCCACAGG 4 91.00 1.30E−02 3′ss Mel. 57193182-57193461 57193143-57193461 GCAGGCTGGAAGGCAGGCTGACTG GCTGGGATGCAT CAAAGCCCAGGA GGGA (1091) TGAG (1092) 737chr11: chr11: TCAGAAGAGAAA TCAGAAGAGAAA 3 7 1.00 3.02E−02 3′ss Mel.66105278-66105713 66105360-66105713 ATCGGATGACAG ATCGGATGGACCGCGGACCCACAG TTGACCCTGCTG GCCC (1093) TTCA (1094) 738 chr7: chr7:TGACTGCCGCTT CTAAAGCCTTCT 3 7 1.00 2.44E−02 exon Mel. 44251203-4425184544250723-44251845 TCTCTCAGGCCC ATAAAACTGCCC incl. GGAAACAAAACTGGAAACAAAACT CATG (1095) CATG (1096) 739 chr12: chr12: ATGCAGATACACATGCAGATACAC 2 5 1.00 1.43E−02 exon Mel. 57925889-5792635457926098-57926354 AAAGCAAGCCAT AAAGCAAGGTGC skip GCAGTTTGGTCAACCAGCTATATG GCTC (1097) AAAC (1098) 740 chr4: chr4: TACTGATCATATAAGAGTGCCAAA 2 5 1.00 2.55E−03 exon Mel. 48853992-4886274148859382-48862741 TGTCCAAGTCAA AAAAGAAGTCAA skip AGTAAACAAGTAAGTAAACAAGTA TGGA (1099) TGGA (1100) 741 chr2: chr2: TGTCATCCATTGTGTCATCCATTG 1 3 1.00 2.77E−02 3′ss Mel. 27604588-2760499227604672-27604992 TGGAAGAGCCCC TGGAAGAGCTGC GAAACACAGCAG TGGATCAGTGCCAGCT (1101) TGGC (1102) 742 chr6: chr6: TACCGGAAACCT GCTGCCAAAGCC 1 31.00 4.97E−02 5′ss Mel. 133136363-133137599 133136227-133137599AGGAAAAGGCGC TTAGACAAGCGC CAAGCCCATCTT CAAGCCCATCTT TGTG (1103) TGTG(1104) 743 chr12: chr12: GGGTGCAAAAGA GGGTGCAAAAGA 0 1 1.00 8.93E−033′ss Mel. 57032980-57033763 57033091-57033763 TCCTGCAGCCAT TCCTGCAGGACTTCCAGGTTGCTG ACAAATCCCTCC AGGT (283) AGGA (284) 744 chr14: chr14:AGGATATCGGTT AGGATATCGGTT 0 1 1.00 1.46E−02 3′ss Mel. 50044571-5005266750050393-50052667 TCATTAAGAAAG TCATTAAGTTGG ACCTGAGCTGTC ACTAAATGCTCTTTCC (1105) TCCT (1106) 745 chr16: chr16: GCGGCGGGCAGT GCGGCGGGCAGT 0 11.00 1.39E−02 3′ss Mel. 85833358-85834789 85833358-85834810 GGCGGCAGGTGTGGCGGCAGAATG ACATTTTTATCT TTGGCTACCAGG TTCA (1107) GTAT (1108) 746chr19: chr19: TATCCAGCACTG CCTGATTCTCCC 0 1 1.00 3.56E−02 exon Mel.35647877-35648323 35646514-35648323 ACCACATGGACA CACCAGAGGACA incl.GACGTTGAAAGA GACGTTGAAAGA TACC (1109) TACC (1110) 747 chr21: chr21:TTCATCATGGTG TTCATCATGGTG 0 1 1.00 1.84E−02 3′ss Mel. 27254101-2726403327254082-27264033 TGGTGGAGCTCT TGGTGGAGGTTG CCTCTTGTTTTT ACGCCGCTGTCACAGG (1111) CCCC (1112) 748 chr21: chr21: TGAAATCAGAAA TGAAATCAGAAA 0 11.00 3.04E−02 3′ss Mel. 46271557-46275124 46271542-46275124 AAAATATGTTTAAAAATATGGCCT TTTTGTTTCAGG GTTTAAAGAAGA CCTG (1113) AAAC (1114) 749 chr3:chr3: CAACGAGAACAA CAACGAGAACAA 0 1 1.00 4.76E−04 3′ss Mel.101401353-101401614 101401336-101401614 GCTATCAGTTAC GCTATCAGGGCTTTTTACCCCACA GCTAAGGAAGCA GGGC (297) AAAA (298) 750 chr4: chr4:CCATGGTCAAAA CCATGGTCAAAA 0 1 1.00 4.92E−05 3′ss Mel.152022314-152024139 152022314-152024022 AATGGCAGCACC AATGGCAGACAAAACAGGTCCGCC TGATTGAAGCTC AAAT (344) ACGT (345) 751 chr9: chr9:GCAAGGATATAT GCAAGGATATAT 0 1 1.00 4.68E−04 3′ss Mel. 86593213-8659328786593194-86593287 AATAACTGCTGC AATAACTGATTG TTTATTTTTCCA GTGTGCCCGTTTCAGA (1115) AATA (1116) 752 chr4: chr4: GAACTGCAAAGG AGTGAATGTAGT 27 540.97 4.49E−02 exon Mel. 169911479-169919352 169911479-169923221CTTCAGAGGATT TGCACCAGGATT incl. TGTACACACAGA TGTACACACAGA TATG (1117)TATG (1038) 753 chrX: chrX: TTGGAGATCAGG GATCTGGATTCT 21 42 0.972.52E−02 5′ss Mel. 102940188-102942916 102940188-102941558 ACGCAAAGGTCACGTTTCAGGTCA CCATCAGAAAAG CCATCAGAAAAG CTAA (1118) CTAA (1119) 754 chr5:chr5: TGGAAGAGGCTA TGGAAGAGGCTA 13 26 0.95 2.18E−02 exon Mel.137503767-137504910 137504377-137504910 CCTCTGGGGTCA CCTCTGGGGTAA skipATGAGAGTGAAA CCCCCGGGACTT TGGC (1120) TGCC (1121) 755 chr13: chr13:TCTGGAGCCATA TCTGGAGCCATA 11 22 0.94 4.45E−02 exon Mel.114291015-114294434 114291015-114292132 CGTGACAGTGAC CGTGACAGAAAT skipCTGACCAACGGT GGCTCAGGGAAC GCAG (1122) TGTT (1123) 756 chr16: chr16:CATCAAGCAGCT CATCAAGCAGCT 11 22 0.94 4.68E−04 3′ss Mel.57473207-57474683 57473246-57474683 GTTGCAATGTTT GTTGCAATCTGCAGTCCCAGGAAG CCACAAAGAATC CACC (822) CAGC (823) 757 chr22: chr22:CTGCAGTATCTG CTGCAGTATCTG 28 52 0.87 1.79E−02 3′ss Mel.31724845-31731677 31724910-31731677 TAACCGAGGTCT TAACCGAGGTTTCCAGGCACCAGG CTCCTCTGCCTC AGCC (1124) CTAC (1125) 758 chrX: chrX:ACTAATCTTCAG CAAACACCTCTT 14 26 0.85 1.55E−02 exon Mel.123224814-123227867 123224614-123227867 CATGCCATTCGG GATTATAATCGG incl.CGTGGCACAAGC CGTGGCACAAGC CTAA (456) CTAA (457) 759 chr7: chr7:TGATTTCAAGTT TGATGAGACTCC 56 100 0.83 5.42E−03 exon Mel. 5028808-50362405035213-5036240 TGAACAAGGGGT AGACAGAGGGGT skip TGGCATCTGCAC TGGCATCTGCACATCC (1126) ATCC (1127) 760 chr8: chr8: AGCGAGCTCCTC CCGGGGATTGCC 29 520.82 4.95E−02 5′ss Mel. 146076780-146078756 146076780-146078377AGCCTCAGGCAT GGCGCCAGGCAT CTGCATCTGGGA CTGCATCTGGGA CCGA (1128) CCGA(1129) 761 chr5: chr5: AGTTTCTACTAG AGTTTCTACTAG 7 13 0.81 3.69E−03 exonMel. 139909381-139916922 139909381-139914946 TCCAGTTGGTGA TCCAGTTGGGTTskip CTCTCCTATTCC ACCATCCATTGA ATCT (1130) CCCA (1131) 762 chr1: chr1:CATAGTGGAAGT CATAGTGGAAGT 42 69 0.70 1.02E−05 3′ss Mel.67890660-67890765 67890642-67890765 GATAGATCTTCT GATAGATCTGGCTTTTCACATTAC CTGAAGCACGAG AGTG (444) GACA (445) 763 chr22: chr22:GGAAAGGACAGC TGAGGTGCCCTA 40 65 0.69 3.49E−02 exon Mel.42557364-42564614 42557364-42565852 AAGCACAGGTGA AGCACAAGGTGA incl.GACTGTGGAGAT GACTGTGGAGAT GAGA (1132) GAGA (1133) 764 chr6: chr6:AGTTGCATGTTG AGTTGCATGTTG 4 7 0.68 3.75E−03 exon Mel. 30587766-3059265930587766-30590608 ACTTTAGGGAGT ACTTTAGGAACG skip CTGTGTGAAGCATGAAGCTCTTGG GCAC (1134) AGCA (1135) 765 chr19: chr19: CCGCCCCCGTTCCCGCCCCCGTTC 41 65 0.65 1.89E−02 3′ss Mel. 2112966-21133342112930-2113334 CATCCACGGGGG CATCCACGGACG AGCTCAGTGTGA AGTGTGAGGACG ACAC(1136) CCAA (1137) 766 chr16: chr16: TGGAGCCGAACA TGGAGCCGAACA 8 13 0.644.20E−03 3′ss Mel. 89960266-89961490 89960266-89961445 ACATCGTGCTCAACATCGTGGTTC GCGATGCCTGCC TGCTCCAGACGA GCTT (1138) GCCC (1139) 767chr10: chr10: TGACGTTCTCTG TGACGTTCTCTG 47 73 0.62 1.42E−03 3′ss Mel.75554088-75554298 75554088-75554313 TGCTCCAGTGGT TGCTCCAGGTTCTTCTCCCACAGG CCGGCCCCCAAG TTCC (466) TCGC (467) 768 chr12: chr12:GCCTGGAAAGCT GCCTGGAAAGCT 28 42 0.57 1.37E−03 3′ss Mel. 6675490-66756946675502-6675694 ACCAAAAGGAGC ACCAAAAGGGAT TGTCCAGACAGC CTCTGCAGGAGC TGGT(1140) TGTC (1141) 769 chr11: chr11: TGTTATTGTAGA TGTTATTGTAGA 37 550.56 4.34E−05 3′ss Mel. 85693031-85694908 85693046-85694908 TTCTGGGGGTGGTTCTGGGGGCTT ACTTCTCAAACC TGATGAACTAGG AACA (1142) TGGA (1143) 770 chr2:chr2: GGGGACCAAGAA GGGGACCAAGAA 59 86 0.54 2.26E−02 exon Mel.55530288-55535944 55529208-55535944 AAGCAGCATGGT AAGCAGCACCAT incl.TGCACTGAAAAG GAATGACCTGGT ACTG (1144) GCAG (1145) 771 chr12: chr12:CAAAAAAGACCA CAAAAAAGACCA 13 19 0.51 2.94E−02 3′ss Mel. 7043741-70447127043741-7044709 AAACTGAGGAAC AAACTGAGCAGG TCCCTCGGCCAC AACTCCCTCGGC AGTC(1146) CACA (1147) 772 chr1: chr1: CCAAAGCAGAGA CCAAAGCAGAGA 9 13 0.493.58E−02 3′ss Mel. 40209596-40211085 40209596-40211046 CCCAGGAGGTGTCCCAGGAGGGAG ACATGGACATCA AGCCCATTGCTA AGAT (1148) AAAA (1149) 773 chr4:chr4: ACTGGGCTTCCA ACTGGGCTTCCA 63 86 0.44 9.76E−04 exon Mel.54266006-54280781 54266006-54292038 CCGAGCAGAAAC CCGAGCAGGAGA incl.AGCACTTCTTCT TTACCTGGGGCA CAGT (848) ATTG (849) 774 chr20: chr20:TGCCTAAGGCGG TGCCTAAGGCGG 61 83 0.44 3.34E−02 3′ss Mel.30310151-30310420 30310133-30310420 ATTTGAATCTCT ATTTGAATAATCTTCTCTCCCTTC TTATCTTGGCTT AGAA (479) TGGA (480) 775 chr4: chr4:GCCGAATCACCT ACTGGGCTTCCA 63 84 0.41 3.70E−03 exon Mel.54280889-54292038 54266006-54292038 GATCTAAGGAGA CCGAGCAGGAGA incl.TTACCTGGGGCA TTACCTGGGGCA ATTG (1150) ATTG (849) 776 chr1: chr1:ACGCCGCAAGTC AGCACCCATGGG 66 87 0.39 2.24E−02 exon Mel.47024472-47025905 47024472-47027149 CTCCAGAGGAAC TGCAGGGGGAAC incl.AGCAGCACAATG AGCAGCACAATG GACC (1151) GACC (1152) 777 chr1: chr1:AACCAGTAACAA AACCAGTAACAA 59 76 0.36 1.42E−02 3′ss Mel.150249040-150252050 150249040-150252053 CGGAACCTCAGA CGGAACCTAGTCGTCCAGATCTGA CAGATCTGAACG ACGA (1153) ATGC (1154) 778 chr20: chr20:GAGACCGCGTGC GAGACCGCGTGC 70 90 0.36 3.80E−03 3′ss Mel.62577996-62587612 62577993-62587612 GAGGACCGCAGC GAGGACCGCAATAATGCAGAGTCC GCAGAGTCCCTG CTGG (1155) GACA (1156) 779 chr1: chr1:GTCTCTGGCAAG GTCTCTGGCAAG 78 100 0.35 3.86E−02 3′ss Mel.211836994-211840447 211836970-211840447 TAATCCAGAACT TAATCCAGTAATTCTTAATCTTCC TAAGAAGAAAGT ATCC (1157) TCAT (1158) 780 chr3: chr3:AAGCATGTAGAA AAGCATGTAGAA 44 56 0.34 4.73E−02 3′ss Mel.133305566-133306002 133305566-133306739 AGCCGGAACAGG AGCCGGAAGGATTACTTAAAATGA AAAGAAATGGAG ATGC (1159) AAGA (1160) 781 chr1: chr1:AGCACCCATGGG AGCACCCATGGG 69 87 0.33 4.36E−02 exon Mel.47025949-47027149 47024472-47027149 TGCAGGGGCAAG TGCAGGGGGAAC incl.CTCCAGAAAAGG AGCAGCACAATG GACT (1161) GACC (1152) 782 chr1: chr1:TCCACAAGAGCG AGGCGGTGAGTG 46 58 0.33 4.32E−02 5′ss Mel.17330906-17331201 17330906-17331186 AGGAGGCGAAGC TCGGACAGAAGCGGGTGCTGCGGT GGGTGCTGCGGT ATTA (1162) ATTA (1163) 783 chr1: chr1:TCCGCCCCACAG GGCGGAGACATG 74 91 0.29 8.93E−03 5′ss Mel.155917806-155920089 155917806-155920059 TCCACGAGACTT GACCAGAGACTTTACCAGAATGCA TACCAGAATGCA GGAC (1164) GGAC (1165) 784 chr17: chr17:TTGATCTTCGGC TTGATCTTCGGC 72 84 0.22 4.78E−02 3′ss Mel.38080478-38083736 38080473-38083736 CCCACACGAACA CCCACACGCAGAGCAGAGAGGGGC GAGGGGCAGCAG AGCA (1166) GATG (1167) 785 chr2: chr2:GAAAAACTTTCC GAAAAACTTTCC 81 94 0.21 4.90E−02 3′ss Mel.242590750-242592926 242590750-242592721 AGCCATTGGGGG AGCCATTGGAGGGACAGGCCCCAC TTGTCGGGACAT CTCG (1168) TTCA (1169) 786 chr9: chr9:GCGCTCGCCCGG CCGCAGGATACC 76 86 0.18 2.12E−02 5′ss Mel.37422830-37424841 37422802-37424841 GCGGCAGACTGT CGCCGAGGCTGTGAGGTGGAGCAG GAGGTGGAGCAG TGGG (1170) TGGG (1171) 787 chr20: chr20:CGGGACGACTTC GCAGCATCTGCC 78 86 0.14 3.03E−02 exon Mel.32661672-32663679 32661441-32663679 TACGACAGGCTC ATATACAGGCTC incl.TTCGACTACCGG TTCGACTACCGG GGCC (1172) GGCC (1173) 788 chr3: chr3:ACTGAAGCAGCA ACTGAAGCAGCA 92 98 0.09 3.80E−03 3′ss Mel.184084588-184085964 184084588-184085900 ACACGCCTCTCT ACACGCCTGCTGGCGTACGTGTCC AGATTGAGAGCT TATG (1174) GCTG (1175) 789 chr19: chr19:CTGCCGGCGGAG CTGCCGGCGGAG 93 99 0.09 7.19E−03 3′ss Mel.58817582-58823531 58817582-58823562 AATATAAGGAGA AATATAAGGTGTTGGACAAACCGT GTGTGACCATGG GTGG (1176) AACG (1177) 790 chr5: chr5:CAACCTCTAAGA CAACCTCTAAGA 97 99 0.03 2.75E−02 3′ss Mel.179225591-179225927 179225576-179225927 CTGGAGCGGTTC CTGGAGCGTGGGTTCTTCCGCAGT AACATCGAGCAC GGGA (1178) CCGG (1179)

Certain splice variants are associated with more than one disease, andthus appear in Table 1 more than one time. In certain instances, splicevariants associated with more than one cancer type may have differentexpression levels in each disease, so there may be more than one set ofexpression data for a given splice variant. Variants differentiallyexpressed across all tested cancer types can be used to evaluate cellshaving SF3B1 neomorphic mutations in additional cancer types. Suchvariants are shown in the following rows of Table 1 (triplicatesrepresent the same splice junction, measured in different cancer types):[13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28,350, 573], [229, 762, 467], [240, 508, 767], [7, 356, 524], [76, 374,596], [35, 547, 280], [84, 364, 571], [85, 564, 297], [24, 597, 296],[21, 372, 545], [36, 576, 407], [105, 423, 639], [62, 580, 447], [31,279, 528], [235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72,640], [48, 343, 554], [360, 65, 540], [178, 329, 750], [71, 265, 556],[15, 283, 530], [18, 267, 583], [129, 418, 622], [333, 25, 541], [247,500, 774], [259, 5, 542], [152, 438, 615], [292, 1, 517], [81, 543,443], [347, 70, 592], [91, 431, 617], [30, 298, 582], [17, 334, 602],[16, 276, 559], [51, 426, 548], [118, 401, 566], [83, 435, 574], and[269, 45, 546]. In certain embodiments, variants that are nonspecific toa particular cancer type can be chosen from the following rows of Table1: [13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28,350, 573], [240, 508, 767], [7, 356, 524], [84, 364, 571], [24, 597,296], [21, 372, 545], [105, 423, 639], [62, 580, 447], [31, 279, 528],[235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72, 640], [360,65, 540], [178, 329, 750], [71, 265, 556], [15, 283, 530], [18, 267,583], [247, 500, 774], [152, 438, 615], [292, 1, 517], [81, 543, 443],[91, 431, 617], [30, 298, 582], [16, 276, 559], or [51, 426, 548].

Certain embodiments of the invention provide splice variants as markersfor cancer. In certain circumstances, cancer cells with a neomorphicSF3B1 protein demonstrate differential expression of certain splicevariants compared to cells without a neomorphic SF3B1 protein. Thedifferential expression of one or more splice variants therefore may beused to determine whether a patient has cancer with a neomorphic SF3B1mutation. In certain embodiments, the patient is also determined to havea cancer cell having a mutant SF3B1 protein. In these methods, one ormore of the splice variants listed in Table 1 can be measured todetermine whether a patient has cancer with a neomorphic SF3B1 mutation.In certain embodiments, one or more aberrant splice variants from Table1 are measured. In other embodiments, one or more canonical splicevariants are measured. Sometimes, both aberrant and canonical variantsare measured.

In some embodiments, one or more aberrant splice variants selected fromrows 260, 262, 263, 265, 266, 267, 272, 273, 275, 276, 277, 279, 281,282, 286, 287, 288, 290, 294, 295, 296, 298, 299, 301, 302, 304, 305,306, 308, 310, 312, 313, 315, 316, 318, 320, 321, 322, 323, 324, 325,326, 327, 328, 329, 330, 331, 335, 337, 339, 342, 346, 348, 349, 350,352, 353, 354, 355, 356, 357, 358, 362, 363, 365, 366, 368, 369, 370,372, 375, 377, 378, 379, 380, 381, 382, 383, 384, 387, 388, 389, 390,391, 392, 393, 394, 397, 398, 400, 402, 403, 404, 405, 406, 413, 415,416, 417, 419, 420, 421, 424, 425, 428, 429, 430, 431, 432, 433, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 454, 455, 456, 458, 459, 460, 461, 462, 464, 465, 468, 469,471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 483, 484, 485, 486,487, 488, 490, 491, 494, 496, 497, 498, 500, 501, 502, 503, 504, 505,506, 507, 508, 509, 510, 511, 513, 514, 515, or 516 of Table 1 can bemeasured in a patient suspected of having CLL. In additionalembodiments, a patient suspected of having CLL can be identified bymeasuring the amounts of one or more of the following aberrant splicevariants listed in Table 1: row 259, 269, 270, 271, 274, 278, 280, 282,292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360, 361, 371,373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434, 439, 443,447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467, 468, 469,470, 472, 479, 482, or 489. In additional embodiments, a patientsuspected of having CLL can be identified by measuring the amounts ofone or more of the following aberrant splice variants listed in Table 1:row 282, 292, 296, 302, 306, 330, 331, 343, 355, 360, 373, 378, 390,391, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 458, 459,460, 462, 463, 466, 468, 469, 470, 472, 479, 482, or 489. In stillfurther embodiments, a patient suspected of having CLL can be identifiedby measuring the amount of one or more of the following aberrant splicevariants listed in Table 1: row 282, 296, 302, 306, 330, 331, 355, 378,390, 391, 424, 425, 433, 439, 443, 447, 448, 451, 452, 458, 459, 460,462, 468, 469, or 472.

In other embodiments, one or more aberrant splice variants selected fromrows 2, 3, 4, 7, 9, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 27, 28,30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 50, 52, 53,54, 56, 57, 58, 61, 62, 63, 64, 66, 67, 68, 71, 72, 75, 77, 78, 79, 80,81, 82, 84, 87, 88, 89, 90, 91, 92, 94, 95, 97, 98, 99, 100, 101, 103,104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 119, 120,121, 122, 123, 124, 125, 126, 127, 131, 132, 133, 134, 135, 136, 138,139, 140, 141, 142, 143, 144, 146, 147, 150, 152, 154, 155, 156, 157,159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,177, 178, 179, 180, 181, 182, 183, 185, 186, 187, 188, 189, 190, 191,192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219,220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 235,236, 237, 238, 239, 240, 241, 242, 243, 244, 247, 249, 250, 251, 252,253, 254, 255, 256, or 257 of Table 1 can be measured in a patientsuspected of having breast cancer. In additional embodiments, a patientsuspected of having breast cancer can be identified by measuring theamounts of one or more of the following aberrant splice variants listedin Table 1: row 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166. Inadditional embodiments, a patient suspected of having breast cancer canbe identified by measuring the amounts of one or more of the followingaberrant splice variants listed in Table 1: row 7, 8, 9, 10, 26, 48, 66,105, 121, 135, or 136. In still further embodiments, a patient suspectedof having breast cancer can be identified by measuring the amount of oneor more of the following aberrant splice variants listed in Table 1: row7, 9, 10, 66, 121, 135, or 136.

In further embodiments, one or more aberrant splice variants selectedfrom rows 518, 519, 520, 521, 523, 524, 525, 526, 527, 528, 529, 531,533, 534, 536, 537, 538, 539, 543, 544, 545, 549, 551, 552, 553, 555,556, 557, 558, 559, 560, 561, 562, 563, 565, 567, 568, 569, 570, 572,573, 575, 577, 578, 579, 580, 581, 582, 583, 584, 585, 588, 589, 590,591, 593, 595, 597, 598, 599, 600, 601, 603, 604, 605, 606, 607, 608,609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 623,625, 627, 628, 629, 630, 632, 634, 635, 636, 637, 638, 640, 641, 643,644, 645, 646, 647, 648, 649, 650, 651, 652, 654, 657, 658, 659, 661,662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675,676, 677, 678, 680, 682, 683, 684, 685, 686, 687, 688, 689, 690, 692,694, 696, 697, 698, 699, 700, 701, 702, 703, 705, 706, 707, 708, 709,710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723,724, 725, 726, 727, 728, 730, 731, 732, 733, 734, 735, 736, 737, 738,739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 750, 751, 752, 753,754, 755, 756, 757, 758, 759, 760, 763, 764, 765, 766, 767, 768, 770,771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784,785, 786, 787, 788, 789, or 790 of Table 1 can be measured in a patientsuspected of having melanoma. In additional embodiments, a patientsuspected of having melanoma can be identified by measuring the amountsof one or more of the following aberrant splice variants listed in Table1: row 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655, 670,679, 680, 727, 729, or 730. In additional embodiments, a patientsuspected of having melanoma can be identified by measuring the amountsof one or more of the following aberrant splice variants listed in Table1: row 519, 521, 522, 535, 554, 587, 601, 618, 639, 654, 670, 680, 727,or 730. In still further embodiments, a patient suspected of havingmelanoma can be identified by measuring the amount of one or more of thefollowing aberrant splice variants listed in Table 1: row 519, 521, 601,618, 654, 670, 680, 727, or 730.

In some embodiments, one or more of the aberrant variants are selectedfrom rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545,548 or 566 of Table 1. In certain embodiments, a patient suspected ofhaving cancer can be identified by measuring the amount of one or moreof the aberrant variants selected from 21, 31, 51, 81, 118, 279, 372,401, 426, 443, 528, 543, 545, 548 or 566. In various embodiments thecancer may be CLL, breast cancer, or melanoma, for example.

Additional methods include predicting or monitoring the efficacy of atreatment for cancer by measuring the level of one or more aberrantsplice variants in samples obtained from patients before or during thetreatment. For example, a decrease in the levels of one or more aberrantsplice variants over the course of treatment may indicate that thetreatment is effective. In other cases, the absence of a decrease or anincrease in the levels of one or more aberrant splice variants over thecourse of treatment may indicate that the treatment is not effective andshould be adjusted, supplemented, or terminated. In some embodiments,the splice variants are used to track and adjust individual patienttreatment effectiveness.

Embodiments of the invention also encompass methods of stratifyingcancer patients into different categories based on the presence orabsence of one or more particular splice variants in patient samples orthe detection of one or more particular splice variants at levels thatare elevated or reduced relative to those in normal cell samples.Categories may be different prognostic categories, categories ofpatients with varying rates of recurrence, categories of patients thatrespond to treatment and those that do not, and categories of patientsthat may have particular negative side effects, and the like. Accordingto the categories in which individual patients fall, optimal treatmentsmay then be selected for those patients, or particular patients may beselected for clinical trials.

Embodiments also encompass methods of distinguishing cancerous cellswith SF3B1 neomorphic mutations from normal cells by using the splicevariants disclosed herein as markers. Such methods may be employed, forexample, to assess the growth or loss of cancerous cells and to identifycancerous cells to be treated or removed. In some embodiments, thesplice variants are measured in cancerous tissue having cells with aneomorphic SF3B1 mutation before and after anti-cancer treatment, forthe purpose of monitoring the effect of the treatment on cancerprogression.

In additional embodiments, administering an SF3B1 modulator to a cell,such as a cancer cell, can alter the differential expression of splicevariants. Accordingly, the change in expression of one or more splicevariants can be used to evaluate the effect of the SF3B1 modulator onthe SF3B1 protein. In one embodiment, the effect of an SF3B1 modulatoron a CLL cell is evaluated by applying an SF3B1 modulator to such acell, then detecting or quantifying one or more of the splice variantsin Table 1. In additional embodiments the one or more splice variantsare chosen from rows 258-516 of Table 1. In further embodiments, the oneor more splice variants are chosen from rows 260, 262, 263, 265, 266,267, 272, 273, 275, 276, 277, 279, 281, 282, 286, 287, 288, 290, 294,295, 296, 298, 299, 301, 302, 304, 305, 306, 308, 310, 312, 313, 315,316, 318, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331,335, 337, 339, 342, 346, 348, 349, 350, 352, 353, 354, 355, 356, 357,358, 362, 363, 365, 366, 368, 369, 370, 372, 375, 377, 378, 379, 380,381, 382, 383, 384, 387, 388, 389, 390, 391, 392, 393, 394, 397, 398,400, 402, 403, 404, 405, 406, 413, 415, 416, 417, 419, 420, 421, 424,425, 428, 429, 430, 431, 432, 433, 436, 437, 438, 439, 440, 441, 442,443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 454, 455, 456, 458,459, 460, 461, 462, 464, 465, 468, 469, 471, 472, 473, 474, 475, 476,477, 478, 480, 481, 483, 484, 485, 486, 487, 488, 490, 491, 494, 496,497, 498, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511,513, 514, 515, or 516 of Table 1. In further embodiments, the one ormore splice variants are chosen from rows 259, 269, 270, 271, 274, 278,280, 282, 292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360,361, 371, 373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434,439, 443, 447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467,468, 469, 470, 472, 479, 482, or 489. In additional embodiments, the oneor more splice variants are chosen from rows 282, 292, 296, 302, 306,330, 331, 343, 355, 360, 373, 378, 390, 391, 423, 424, 425, 433, 434,439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 463, 466, 468, 469,470, 472, 479, 482, or 489 of Table 1. In still further embodiments, theone or more splice variants are chosen from rows 282, 296, 302, 306,330, 331, 355, 378, 390, 391, 424, 425, 433, 439, 443, 447, 448, 451,452, 458, 459, 460, 462, 468, 469, or 472 of Table 1.

In certain embodiments, the effect of an SF3B1 modulator on a breastcancer cell is evaluated by applying an SF3B1 modulator to such a cell,then detecting or quantifying one or more of the splice variants inTable 1. In additional embodiments the one or more splice variants arechosen from rows 1-257 of Table 1. In further embodiments, the one ormore splice variants are chosen from rows 2, 3, 4, 7, 9, 10, 11, 13, 16,18, 19, 20, 21, 22, 23, 24, 27, 28, 30, 31, 32, 33, 34, 37, 38, 39, 40,41, 42, 43, 46, 47, 49, 50, 52, 53, 54, 56, 57, 58, 61, 62, 63, 64, 66,67, 68, 71, 72, 75, 77, 78, 79, 80, 81, 82, 84, 87, 88, 89, 90, 91, 92,94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 107, 108, 109, 110, 111,112, 113, 114, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127,131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 146,147, 150, 152, 154, 155, 156, 157, 159, 163, 164, 165, 167, 168, 169,170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 230, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242,243, 244, 247, 249, 250, 251, 252, 253, 254, 255, 256, or 257 ofTable 1. In additional embodiments, the one or more splice variants arechosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166 ofTable 1. In further embodiments, the one or more splice variants arechosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, or 136 ofTable 1. In still further embodiments, the one or more splice variantsare chosen from rows 7, 9, 10, 66, 121, 135, or 136 of Table 1.

In a further embodiment, the effect of an SF3B1 modulator on a melanomacell is evaluated by applying an SF3B1 modulator to such a cell, thendetecting or quantifying one or more of the splice variants in Table 1.In additional embodiments the one or more splice variants are chosenfrom rows 517-790 of Table 1. In further embodiments, the one or moresplice variants are chosen from rows 518, 519, 520, 521, 523, 524, 525,526, 527, 528, 529, 531, 533, 534, 536, 537, 538, 539, 543, 544, 545,549, 551, 552, 553, 555, 556, 557, 558, 559, 560, 561, 562, 563, 565,567, 568, 569, 570, 572, 573, 575, 577, 578, 579, 580, 581, 582, 583,584, 585, 588, 589, 590, 591, 593, 595, 597, 598, 599, 600, 601, 603,604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617,618, 619, 620, 621, 623, 625, 627, 628, 629, 630, 632, 634, 635, 636,637, 638, 640, 641, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652,654, 657, 658, 659, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670,671, 672, 673, 674, 675, 676, 677, 678, 680, 682, 683, 684, 685, 686,687, 688, 689, 690, 692, 694, 696, 697, 698, 699, 700, 701, 702, 703,705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718,719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 730, 731, 732, 733,734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747,748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 763, 764,765, 766, 767, 768, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779,780, 781, 782, 783, 784, 785, 786, 787, 788, 789, or 790 of Table 1. Instill further embodiments, the one or more splice variants are chosenfrom rows 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655,670, 679, 680, 727, 729, or 730 of Table 1. In additional embodiments,the one or more splice variants are chosen from rows 519, 521, 522, 535,554, 587, 601, 618, 639, 654, 670, 680, 727, or 730 of Table 1. In stillfurther embodiments, the one or more splice variants are chosen fromrows 519, 521, 601, 618, 654, 670, 680, 727, or 730 of Table 1.

In some embodiments, the effect of an SF3B1 modulator on a cancer cellis evaluated by applying an SF3B1 modulator to such a cell, thendetecting or quantifying one or more of the aberrant variants selectedfrom rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545,548 or 566 of Table 1. In various embodiments, the cancer cell may be aCLL cell, a breast cancer cell, or a melanoma cell, for example.

The specific splice variants that are useful for demonstrating theeffect of an SF3B1 modulator on one type of cancer cell may not beuseful for demonstrating an effect of the modulator on another type ofcancer cell. Aberrant splice variants that are appropriate for revealingsuch effects in particular cancer cells will be apparent from thedescription and examples provided herein.

In some embodiments, aberrant splice variants that are present atelevated levels in a cell having a neomorphic SF3B1 protein are used asmarkers. In other embodiments, splice variants that have reduced levelsin a cell having a neomorphic SF3B1 protein are used as markers. In someembodiments, more than one splice variant will be measured. When morethan one splice variant is used, they may all have elevated levels, allhave reduced levels, or a mixture of splice variants with elevated andreduced levels may be used. In certain embodiments of the methodsdescribed herein, more than one aberrant splice variant is measured. Inother embodiments, at least one aberrant and at least one canonicalsplice variant is measured. In some cases, both an aberrant andcanonical splice variant associated with a particular genomic locationwill be measured. In other circumstances, a measured canonical splicevariant will be at a different genomic location from the measuredaberrant splice variant(s).

Before performing an assay for splice variants in a cell, one maydetermine whether the cell has a mutant SF3B1 protein. In certainembodiments, the assay for splice variants is performed if the cell hasbeen determined to have a neomorphic SF3B1 mutant protein.

Samples

Cell samples can be obtained from a variety of biological sources.Exemplary cell samples include but are not limited to a cell culture, acell line, a tissue, oral tissue, gastrointestinal tissue, an organ, anorganelle, a biological fluid, a blood sample, a urine sample, a skinsample, and the like. Blood samples may be whole blood, partiallypurified blood, or a fraction of whole or partially purified blood, suchas peripheral blood mononucleated cells (PBMCs). The source of a cellsample may be a solid tissue sample such as a tissue biopsy. Tissuebiopsy samples may be biopsies from breast tissue, skin, lung, or lymphnodes. Samples may be samples of bone marrow, including bone marrowaspirates and bone marrow biopsies.

In certain embodiments, the cells are human cells. Cells may be cancercells, for example hematological cancer cells or solid tumor cells.Hematological cancers include chronic lymphocytic leukemia, acutelymphoblastic leukemia, acute myeloid leukemia, chronic myeloidleukemia, chronic myelomonocytic leukemia, acute monocytic leukemia,Hodgkin's lymphoma, Non-Hodgkin's lymphoma, and multiple myeloma. Solidtumors include carcinomas, such as adenocarcinomas, and may be selectedfrom breast, lung, liver, prostate, pancreatic, colon, colorectal, skin,ovarian, uterine, cervical, or renal cancers. Cell samples may beobtained directly from a patient or derived from cells obtained from apatient, such as cultured cells derived from a biological fluid ortissue sample. Samples may be archived samples, such as kryopreservedsamples, of cells obtained directly from a subject or of cells derivedfrom cells obtained from a patient.

In certain embodiments, cells are obtained from patients suspected ofhaving cancer. The patients may show signs and symptoms of cancer, suchas one or more common symptoms of CLL, which include enlarged lymphnodes, liver, or spleen, higher-than-normal white blood cell counts,recurring infections, loss of appetite or early satiety, abnormalbruising, fatigue, and night sweats. In additional embodiments, thecells have a mutant SF3B1 protein.

Cell samples described herein may be used in any of the methodspresently disclosed.

Detection of Splice Variants

Certain embodiments of the methods described herein involve detection orquantification of splice variants. A variety of methods exists fordetecting and quantifying nucleic acids, and each may be adapted fordetection of splice variants in the described embodiments. Exemplarymethods include an assay to quantify nucleic acid such as nucleic acidbarcoding, nanoparticle probes, in situ hybridization, microarray,nucleic acid sequencing, and PCR-based methods, including real-time PCR(RT-PCR).

Nucleic acid assays utilizing barcoding technology such as NanoString®assays (NanoString Technologies) may be performed, for example, asdescribed in U.S. Pat. Nos. 8,519,115; 7,919,237; and in Kulkarni, M.M., 2011, “Digital Multiplexed Gene Expression Analysis Using theNanoString nCounter System.” Current Protocols in Molecular Biology,94:25B.10.1-25B.10.17. In an exemplary assay, a pair of probes is usedto detect a particular nucleotide sequence of interest, such as aparticular splice variant of interest. The probe pair consists of acapture probe and a reporter probe and that each include a sequence offrom about 35 to 50 bases in length that is specific for a targetsequence. The capture probe includes an affinity label such as biotin atits 3′ end that provides a molecular handle for surface-attachment oftarget mRNAs for digital detection, and the reporter probe includes aunique color code at its 5′ end that provides molecular barcoding of thehybridized mRNA target sequence. Capture and reporter probe pairs arehybridized to target mRNA in solution, and after excess probes areremoved, the target mRNA-probe complexes are immobilized in an nCounter®cartridge. A digital analyzer acquires direct images of the surface ofthe cartridge to detect color codes corresponding to specific mRNAsplice variant sequences. The number of times a color-coded barcode fora particular splice variant is detected reflects the levels of aparticular splice variant in the mRNA library. For the detection ofsplice variants, either the capture or the reporter probe may span agiven splice variant's exon-exon or intron-exon junction. In otherembodiments, one or both of the capture and reporter probes' targetsequences correspond to the terminal sequences of two exons at anexon-exon junction or to the terminal sequences of an intron and an exonat an intron-exon junction, whereby one probe extends to the exon-exonor intron-exon junction, but does not span the junction, and the otherprobe binds a sequence that begins on opposite side of the junction andextends into the respective exon or intron.

In exemplary PCR-based methods, a particular splice variant may bedetected by specifically amplifying a sequence that contains the splicevariant. For example, the method may employ a first primer specificallydesigned to hybridize to a first portion of the splice variant, wherethe splice variant is a sequence that spans an exon-exon or intron-exonjunction at which alternative splicing occurs. The method may furtheremploy a second opposing primer that hybridizes to a segment of the PCRextension product of the first primer that corresponds to anothersequence in the gene, such as a sequence at an upstream or downstreamlocation. The PCR detection method may be quantitative (or real-time)PCR. In some embodiments of quantitative PCR, an amplified PCR productis detected using a nucleic acid probe, wherein the probe may containone or more detectable labels. In certain quantitative PCR methods, theamount of a splice variant of interest is determined by detecting andcomparing levels of the splice variant to an appropriate internalcontrol.

Exemplary methods for detecting splice variants using an in situhybridization assay such as RNAscope® (Advanced Cell Diagnostics)include those described by Wang, F., et al., “RNAscope: a novel in situRNA analysis platform for formalin-fixed, paraffin-embedded tissues,” J.Mol. Diagn. 2012 January; 14(1):22-9. RNAscope® assays may be used todetect splice variants by designing a pair of probes that targets agiven splice variant, and are hybridized to target RNA in fixed andpermeabilized cells. Target probes are designed to hybridize as pairswhich, when hybridized to the target sequence, create a binding site fora preamplifier nucleic acid. The preamplifier nucleic acid, in turn,harbors multiple binding sites for amplifier nucleic acids, which inturn contain multiple binding sites for a labeled probe carrying achromogenic or fluorescent molecule. In some embodiments, one of theRNAscope® target probes spans a given splice variant's exon-exon orintron-exon junction. In other embodiments, the target probes' targetsequences correspond to the terminal sequences of two exons at anexon-exon junction or to the terminal sequences of an intron and an exonat an intron-exon junction, whereby one probe in the target probe pairextends to the exon-exon or intron-exon junction, but does not span thejunction, and the other probe binds a sequence beginning on oppositeside of the junction and extending into the respective exon or intron.

Exemplary methods for detecting splice variants using nanoparticleprobes such as SmartFlare™ (Millipore) include those described inSeferos et al., “Nano-flares: Probes for Transfection and mRNA Detectionin Living Cells,” J. Am. Chem. Soc. 129(50):15477-15479 (2007) andPrigodich, A. E., et al., “Multiplexed Nanoflares: mRNA Detection inLive Cells,” Anal. Chem. 84(4):2062-2066 (2012). SmartFlare™ detectionprobes may be used to detect splice variants by generating goldnanoparticles that are modified with one or more nucleic acids thatinclude nucleotide recognition sequences that (1) are each complementaryto a particular splice variant to be detected and (2) are eachhybridized to a complementary fluorophore-labeled reporter nucleic acid.Upon uptake of the probe by a cell, a target splice variant sequence mayhybridize to the one or more nucleotide recognition sequences anddisplace the fluorophore-labeled reporter nucleic acid. Thefluorophore-labeled reporter nucleic acid, whose fluorophore had beenquenched due to proximity to the gold nanoparticle surface, is thenliberated from the gold nanoparticle, and the fluorophore may then bedetected when free of the quenching effect of the nanoparticle. In someembodiments, nucleotide recognition sequences in the probes recognize asequence that spans a given splice variant's exon-exon or intron-exonjunction. In some embodiments, nucleotide recognition sequences in theprobes recognize a sequence that is only on one side of the splicevariant's exon-exon or intron-exon junction, including a sequence thatterminates at the junction and a sequence that terminates one or morenucleotides away from the junction.

Exemplary methods for detecting splice variants using nucleic acidsequencing include RNA sequencing (RNA-Seq) described in Ren, S. et al.“RNA-Seq analysis of prostate cancer in the Chinese populationidentifies recurrent gene fusions, cancer-associated long noncoding RNAsand aberrant alternative splicings.” Cell Res 22, 806-821,doi:10.1038/cr.2012.30 (2012); and van Dijk et al., “Ten years ofnext-generation sequencing technology.” Trends Genet 30(9):418-26(2014). In some embodiments, high-throughput sequencing, such asnext-generation sequencing (NGS) technologies, may be used to dectedsplice variants. For example, the method may employ commercialsequencing platforms available for RNA-Seq, such as, e.g., Illumina,SOLID, Ion Torrent, and Roche 454. In some embodiments, the sequencingmethod may include pyrosequencing. For example, a sample may be mixedwith sequencing enzymes and primer and exposed to a flow of oneunlabeled nucleotide at a time, allowing synthesis of the complementaryDNA strand. When a nucleotide is incorporated, pyrophosphate is releasedleading to light emission, which is monitored in real time. In someembodiments, the sequencing method may include semiconductor sequencing.For example, proton instead of pyrophosphate may be released duringnucleotide incorporation and detected in real time by ion sensors. Insome embodiments, the method may include sequencing with reversibleterminators. For example, the synthesis reagents may include primers,DNA polymerase, and four differently labelled, reversible terminatornucleotides. After incorporation of a nucleotide, which is identified byits color, the 3′ terminator on the base and the fluorophore areremoved, and the cycle is repeated. In some embodiments, the method mayinclude sequencing by ligation. For example, a sequencing primer may behybridized to an adapter, with the 5′ end of the primer available forligation to an oligonucleotide hybridizing to the adjacent sequence. Amixture of octamers, in which bases 4 and 5 are encoded by one of fourcolor labels, may compete for ligation to the primer. After colordetection, the ligated octamer may be cleaved between position 5 and 6to remove the label, and the cycle may be repeated. Thereby, in thefirst round, the process may determine possible identities of bases inpositions 4, 5, 9, 10, 14, 15, etc. The process may be repeated, offsetby one base using a shorter sequencing primer, to determine positions 3,4, 8, 9, 13, 14, etc., until the first base in the sequencing primer isreached.

Other nucleic acid detection and analytical methods that alsodistinguish between splice variants of a given exon-exon or intron-exonjunction in a gene by identifying the nucleotide sequence on both sidesof the junction may be utilized to detect or quantify the splicevariants disclosed herein. For example, splice variants of an exon-exonjunction may be detected by primer extension methods in which a primerthat binds to one exon is extended into the exon on the other side ofthe junction according to the sequence of that adjacent exon. See, forexample, McCullough, R. M., et al., “High-throughput alternativesplicing quantification by primer extension and matrix-assisted laserdesorption/ionization time-of-flight mass spectrometry,” Nucleic AcidsResearch, 2005 Jun. 20; 33(11):e99; and Milani, L., et al., “Detectionof alternatively spliced transcripts in leukemia cell lines byminisequencing on microarrays,” Clin. Chem. 52: 202-211 (2006).Detection of variants on a large scale may be performed using expressionmicroarrays that carry exon-exon or intron-exon junction probes, asdescribed, for example, in Johnson, J. M. et al., “Genome-wide survey ofhuman alternative pre-mRNA splicing with exon junction microarrays,”Science 302: 2141-2144 (2003); and Modrek, B., et al., “Genome-widedetection of alternative splicing in expressed sequences of humangenes,” Nucleic Acids Res 29: 2850-2859 (2001).

Various embodiments include reagents for detecting splice variants ofthe invention. In one example, reagents include NanoString® probesdesigned to measure the amount of one or more of the aberrant splicevariants listed in Table 1. Probes for nucleic acid quantificationassays such as barcoding (e.g. NanoString®), nanoparticle probes (e.g.SmartFlare™), in situ hybridization (e.g. RNAscope®), microarray,nucleic acid sequencing, and PCR-based assays may be designed as setforth above.

In these exemplary methods or in other methods for nucleic aciddetection, aberrant splice variants may be identified using probes,primers, or other reagents which specifically recognize the nucleic acidsequence that is present in the aberrant splice variant but absent inthe canonical splice variant. In other embodiments, the aberrant splicevariant is identified by detecting the sequence that is specific to theaberrant splice variant in the context of the junction in which itoccurs, i.e., the unique sequence is flanked by the sequences which arepresent on either side of the splice junction in the canonical splicevariant. In such cases, the portion of the probe, primer, or otherdetection reagent that specifically recognizes its target sequence mayhave a length that corresponds to the length of the aberrant sequence orto or a portion of the aberrant sequence. In other embodiments, theportion of the probe, primer, or other detection reagent thatspecifically recognizes its target sequence may have a length thatcorresponds to the length of the aberrant sequence plus the length of achosen number of nucleotides from one or both of the sequences whichflank the aberrant sequence at the splice junction. Generally, the probeor primer should be designed with a sufficient length to reducenon-specific binding. Probes, primers, and other reagents that detectaberrant or canonical splice variants may be designed according to thetechnical features and formats of a variety of methods for detection ofnucleic acids.

SF3B1 Modulators

A variety of SF3B1 modulating compounds are known in the art, and can beused in accordance with the methods described herein. In someembodiments, the SF3B1 modulating compound is a pladienolide orpladienolide analog. A “pladienolid analog” refers to a compound whichis structurally related to a member of the family of natural productsknown as the pladienolides. Plandienolides were first identified in thebacteria Streptomyces platensis (Sakai, Takashi; Sameshima, Tomohiro;Matsufuji, Motoko; Kawamura, Naoto; Dobashi, Kazuyuki; Mizui, Yoshiharu.“Pladienolides, New Substances from Culture of Streptomyces platensisMer-11107. I. Taxonomy, Fermentation, Isolation and Screening.” TheJournal of Antibiotics. 2004, Vol. 57, No. 3). One of these compounds,pladienolide B, targets the SF3B spliceosome to inhibit splicing andalter the pattern of gene expression (Kotake et al., “Splicing factorSF3b as a target of the antitumor natural product pladienolide”, NatureChemical Biology 3:570-575 [2007]). Certain pladienolide B analogs aredescribed in WO 2002/060890; WO 2004/011459; WO 2004/011661; WO2004/050890; WO 2005/052152; WO 2006/009276; and WO 2008/126918.

U.S. Pat. Nos. 7,884,128 and 7,816,401, both entitled “Process for TotalSynthesis of Pladienolide B and Pladienolide D,” describe methods forsynthesizing pladienolide B and D. Synthesis of pladienolide B and D mayalso be performed using methods described in Kanada et al., “TotalSynthesis of the Potent Antitumor Macrolides Pladienolide B and D,”Angew. Chem. Int. Ed. 46:4350-4355 (2007). Kanada et al., U.S. Pat. No.7,550,503, and International Publication No. WO 2003/099813 (WO '813),entitled “Novel Physiologically Active Substances,” describe methods forsynthesizing E7107 (Compound 45 of WO '813) from pladienolide D (11107Dof WO '813). In some embodiments, the SF3B1 modulator is pladienolide B.In other embodiments, the SF3B1 modulator is pladienolide D. In furtherembodiments, the SF3B1 modulator is E7107.

In some embodiments, the SF3B1 modulator is a compound described in U.S.application Ser. No. 14/710,687, filed May 13, 2015, which isincorporated herein by reference in its entirety. In some embodiments,the SF3B1 modulating compound is a compound having one of formulas 1-4as set forth in Table 2. Table 2. Exemplary SF3B1 modulating compounds.

Compound Structure

1

2

3

4

The methods described herein may be used to evaluate known and novelSF3B1 modulating compounds.

Methods of Treatment

Various embodiments of the invention include treating a patientdiagnosed with cancer using an SF3B1 modulator. In certain instances,cancer cells from the patient have been determined to have a mutantSF3B1 protein. Specific SF3B1 mutants include E622D, E622K, E622Q,E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S,N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y,T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E,V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R,G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. In certainembodiments, SF3B1 mutants are chosen from K700E, K666N, R625C, G742D,R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N,N626Y, T663P, H662R, G740V, D781E, or R625L. In additional embodiments,the cancer cells have been tested to measure the amount of one or moresplice variants selected from Table 1. Specific splice variantsassociated with neomorphic SF3B1 mutations are shown in Table 1 anddescribed in the section on splice variants above.

In certain embodiments, a cancer patient determined to have a mutantSF3B1 protein is treated with an SF3B1 modulator as described in U.S.application Ser. No. 14/710,687, filed May 13, 2015.

EXAMPLES Example 1: SF3B1 Mutations Induce Abnormal Splicing in aLineage-Specific Manner

To investigate splicing alterations associated with SF3B1 mutations(“SF3B1^(MUT)”) across multiple tumor types, an RNA-Seq quantificationand differential splicing pipeline was developed and used to analyzeRNA-Seq profiles from the following samples:

-   -   all SF3B1^(MUT) samples in The Cancer Genome Atlas (TCGA; from        81 patients in all, representing 16 cancer types), and 40 wild        type SF3B1 (SF3B1^(WT)) samples from each of the breast        cancer (20) and melanoma (20) cohorts in TCGA,    -   seven SF3B1^(MUT) and seven SF3B1^(WT) CLL patient samples        obtained from the Lymphoma/Myeloma Service in the Division of        Hematology/Oncology at the New York Weill Cornell Medical        Center.

RNA-Seq Quantification Methods

Splice junctions were quantified directly from alignments (BAM files) tofacilitate discovery of unannotated splice variants. For internallygenerated RNA-Seq data, reads were aligned to the human reference genomehg19 (GRCh37) by MapSplice and quantified by RSEM against the TCGA GAF2.1 isoform and gene definition, emulating the TCGA “RNASeqV2” pipeline.Splice junction counts generated by MapSplice were used for downstreamprocessing. For TCGA RNA-Seq data, comprehensive splice junction countsgenerated by MapSplice were not available; instead TCGA “Level 3” splicejunction data reports mapped read counts for a predefined set of splicejunctions from reference transcriptomes. To reconstruct genome-widesplice junction counts comparable to internally-generated RNA-Seqsamples, raw RNA-Seq alignments (BAM files) were obtained from CGHub andany reads that span across a potential splice junction were directlycounted. RSEM-estimated gene expression read counts were gathereddirectly from the TCGA RNA-SeqV2 Level 3 data matrices.

Because MapSplice only provides exon-exon junction counts, estimates ofread counts spanning each intron-exon junction were required foridentification of intron-retention splice variants. For every splicejunction in each BAM file, reads with at least a 3-bp overhang acrosseach of the 3′ and 5′ intron-exon junctions were counted.

For all manipulation of spliced reads within BAM files, a custom Pythonmodule “splicedbam” was used, which uses the “pysam” extension ofsamtools (Li, H., et al., “The Sequence Alignment/Map format andSAMtools.” Bioinformatics, 2009 Aug. 15; 25(16):2078-9).

In some instances, splice junctions had very low counts, occasionallydue to sequencing and alignment errors. Therefore, only splice junctionsthat had at least a total of 10 counts on average from either SF3B1^(WT)or SF3B1^(1T) cohorts were included in downstream analyses.

Differential Splicing Detection Methods

In order to detect differential usage of a splice variant in one cohortrelative to another, independent of gene expression changes andpre-defined alternative splicing models, a computational differentialsplicing pipeline was developed that converts splice junction countsinto percentages of junction usage at splice sites with multiplepossible junctions. The percentage of junction usage is a measurement ofthe occurrence of one splice variant relative to all other splicevariants that share the same splice site. For instance, a splice variantwith an alternative 3′ splice site must share its 5′ splice site withanother splice variant. Therefore, for each shared splice site, the rawcounts of each splice variant were divided by the total counts of allsplice variants that utilize the shared splice site in order to derive aratio. This ratio was then multiplied by 100 to convert it to apercentage. For each sample, the sum of all of the percentages of splicevariants that share the same splice site will equal 100. Thetransformation of raw counts of each splice variant into a percentage ofall splice variants sharing a splice site is itself a normalization toreduce the effect of gene expression changes. The percentages forcanonical and aberrant junctions are listed in Table 1 as “Avg WT %” and“Avg Ab. %,” respectively. Differences between these percentages wereassessed for statistical significance by using the moderated t-testdefined in the Bioconductor's limma package. The statistical p-valueswere corrected into q values using the Benjamini-Hochberg procedure, andlisted as “FDR Q-Values” in Table 1. Any splice variant that satisfied aq value of less than or equal to 0.05 was considered statisticallysignificant.

The conversion of raw junction counts into percentage junction usage canintroduce noise in some instances, i.e., when a gene in which a splicevariant occurs is expressed in one cohort but has very low expression oris not expressed at all in another cohort. To address this, anadditional filtering step was introduced. For each up-regulated splicevariant in an SF3B1^(MUT) sample that satisfies the above q valuethreshold, its corresponding canonical splice variant must bedown-regulated in the SF3B1^(MUT) sample and also must also satisfy theq value threshold for the up-regulated splice variant to be consideredan aberrant splice variant.

Identification of Aberrant Splice Variants in Neomorphic SF3B1^(MUT)Patient Samples

Initially, this framework was applied to a subset of known SF3B1^(MUT)cancers or wild-type counterparts from The Cancer Genome Atlas (TCGA;luminal A primary breast cancer: 7 SF3B1^(K700E) and 20 SF3B1^(WT);metastatic melanoma: 4 SF3B1^(MUT); and 20 SF3B1^(WT)) and internallygenerated 7 SF3B1^(MUT) and 7 SF3B1^(WT) CLL patient samples. Thisanalysis revealed 626 aberrant splice junctions to be significantlyupregulated in SF3B1^(MUT) compared to SF3B1^(WT). The vast majority ofaberrant splicing events use an alternative 3′ss (see Table 1, “Event”column).

The computational screening of aberrant splicing events revealed apattern of tumor-specific splicing events in breast cancer, melanoma andCLL in neomorphic SF3B1^(MUT) samples (Table 1). In addition, a set oftumor-non-specific events (i.e., splicing events found in at least twotumor types) was observed. Some splice variants of genes withtumor-specific splicing events occur in genes with higher mRNAexpression, indicating that some of the observed tumor-specific splicingresults from gene expression differences (FIG. 2).

To characterize the effect of aberrant splicing in all SF3B1 variantsacross cancer types, RNA-Seq data for the remaining 70 SF3B1^(MUT)patients from 14 cancer types in TCGA were quantified, and anunsupervised clustering analysis was done using all 136 samples. Thisclustering separated splicing events associated with neomorphic SF3B1mutants from those associated with wild-type SF3B1 or non-neomorphicSF3B1 mutants. For example, splicing patterns associated with neomorphicSF3B1 mutants were observed in breast cancer (SF3B1^(K666E),SF3B1^(N626D)), lung adenocarcinoma (SF3B1^(K741N), SF3B1^(G740V)), andbladder cancer (SF3B1^(R625C)) patient samples, as splicing events inthese samples clustered with those in SF3B1^(K700E) neomorphic samples,whereas the splicing profiles for other SF3B1 mutant samples weresimilar to those of SF3B1^(WT) samples of the same tumor type. A listingof SF3B1 mutants whose splicing profiles clustered with those ofneomorphic SF3B1 mutants is provided in Table 3, column 1. AdditionalSF3B1 mutations that are predicted to be neomorphic are listed in Table3, column 2. A schematic diagram showing the locations of all mutationsprovided in Table 3 is shown in FIG. 3.

TABLE 3 Select SF3B1 mutations SF3B1 Mutations with Splicing ProfilesClustering with Neomorphic Predicted Neomorphic SF3B1 Mutations SF3B1Mutations K700E K666Q K666N K666M R625C H662D G742D D781G R625H I704FE622D I704N H662Q V701F K666T R625P K666E R625G K666R N626D G740E H662YY623C N626S T663I G740R K741N N626I N626Y N626H T663P V701I H662R R625SG740V K741T D781E K741Q R625L I704V I704S E622V Y623S Y623H V701A K666SH662L G740K E622Q E622K D781N

Example 2: Validation of Aberrant Splice Variants in Cell Lines

Aberrant splicing in cell line models was analyzed by collecting RNA-Seqprofiles for a panel of cell lines with endogenous SF3B1 neomorphicmutations (pancreatic adenocarcinoma Panc 05.04: SF3B1^(Q699H/K700E)double mutant; metastatic melanoma Colo829: SF3B1^(P718L); and lungcancer NCI-H358: SF3B1^(A745V); obtained from the American Type CultureCollection [ATCC] or RIKEN BioResource Center and cultured asinstructed) and from several SF3B1^(WT) cell lines from either the sametumor types (pancreatic adenocarcinoma Panc 10.05, HPAF-II, MIAPaCa-2,Panc04.03, PK-59, lung cancer NCI-H358, NCI-H1792, NCI-H1650, NCI-H1975,NCI H1838) or normal control cells of the same patient (Epstein-Barrvirus [EBV]-transformed B lymphoblast colo829BL). RNA-Seq profiles werealso collected from isogenic pre B-cell lines (Nalm-6) engineered viaAAV-mediated homology to express SF3B1^(K700E) (Nalm-6 SF3B1^(K700E)) ora synonymous mutation (Nalm-6 SF3B1^(K700K)). The isogenic cell linesNalm-6 SF3B1^(K700E) and Nalm-6 SF3B1^(K700K) generated at HorizonDiscovery, were cultured in presence of Geneticin (0.7 mg/ml, LifeTechnologies) for selection. All RNA-Seq analysis was performed usingthe same pipeline described for patient samples in Example 1.Unsupervised clustering of cell lines using the aberrant splicejunctions identified in patients resulted in clear segregation of Panc05.04 and Nalm-6 SF3B1^(K700E) from wild-type and other SF3B1-mutantcells.

A NanoString® assay was developed to quantify aberrant and canonicalsplice variants and was validated using the same cell panel. For theNanoString® assay, 750 ng of purified total RNA was used as template forthe nCounter® (NanoString Technologies®) expression assay using a custompanel of NanoString® probes. The sample preparation was set up asrecommended (NanoString® Technologies protocol no. C-0003-02) for anovernight hybridization at 65° C. The following day, samples wereprocessed through the automated nCounter® Analysis System Prep Stationusing the high sensitivity protocol (NanoString® Technologies protocolno. MAN-00029-05) followed by processing through the nCounter® AnalysisSystem Digital Analyzer (protocol no. MAN-00021-01) using 1150 FOVs fordetection. Data was downloaded and analyzed for quality control metricsand normalization using the nSolver™ Analysis Software (NanoStringTechnologies®). The data was first normalized for lane-to-lane variationusing the positive assay controls provided by the manufacturer(NanoString® positive controls A-F [containing in vitro transcribed RNAtranscripts at concentrations of 128 fM, 32 fM, 8 fM, 2 fM, 0.5 fM, and0.125 fM, each pre-mixed with NanoString® Reporter CodeSet probes])).Any samples with normalization factors <0.3 and >3 were not consideredfor further analysis. This was followed by content normalization usingthe geo-mean of GAPDH, EEF1A1 and RPLP0. All samples were within therecommended 0.1-10 normalization factor range. Each normalized value wasthen checked to ensure that it was at least two standard deviationshigher than the average of background signal recorded for that lane. Anyvalue below that was considered below detection limit. These normalizedvalues were taken for further bioinformatics and statistical analysis.

As observed in the RNA-Seq analysis, only the Panc 05.04 and isogenicNalm-6 SF3B1^(K700E) cell lines showed clear presence of aberrantsplicing (FIG. 4).

Analysis of SF3B1 Mutant SF3B1Q^(699H)

The Panc 05.04 cell line carries the neomorphic mutation SF3B1^(K700E)and an additional mutation at position 699 (SF3B1^(Q699H)). To evaluatethe functional relevance of this second mutation, SF3B1^(Q699H) andSF3B1^(K700E) mutant SF3B1 proteins were expressed alone or incombination in 293FT cells (FIG. 5) for analysis of RNA by NanoString®.To express the mutants in 293FT cells, mammalian expression plasmidswere generated using the Gateway technology (Life Technologies). First,the HA-tag mxSF3B1 wild-type (Yokoi, A. et al. “Biological validationthat SF3b is a target of the antitumor macrolide pladienolide.” FEBS J.278:4870-4880 [2011]) was cloned by PCR into the pDONR221, then themutations were introduced using the site-directed mutagenesis kit(QuikChange II XL, Agilent). LR reaction was performed to clone all theHA-tag mxSF3B1 wild-type and mutants into the pcDNA-DEST40 (LifeTechnologies). 293FT cells (Life Technologies), cultured according tothe manufacturer's instructions, were seeded on 6 wells/plate andtransfected with generated plasmid using Fugene (Roche). One μg of DNAper pcDNA-DEST40 HA-mxSF3B1 construct was used for each transienttransfection, generated in triplicates. Forty-eight hours aftertransfection, cells were collected to isolate protein and RNA forwestern blot and NanoString® analysis, respectively. Protein extractswere prepared by lysing the cells with RIPA (Boston BioProducts).Twenty-three μg of protein was loaded in a SDS-PAGE gel and identifiedusing SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH (Sigma). Li-Cordonkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit 800CW were used assecondary antibodies and detected by Odyssey imager (Li-Cor). RNA wasisolated from the cells and retrotranscribed using MagMax for Microarrayand Superscript VILO II (Life Technologies), respectively, according tothe manufacturer manual, and then analyzed with the NanoString® assay.

Expression of SF3B1^(K700E) and SF3B1^(Q699H/K700E) induced aberrantsplicing, whereas SF3B1^(Q699H) alone or SF3B1^(A745V) or SF3B1^(R1074H)(a substitution conferring resistance to the spliceosome inhibitorpladienolide B) did not induce aberrant splicing (FIG. 6), indicatingthat SF3B1Q^(999H) is a non-functional substitution.

These data confirm that Panc 05.04 and Nalm-6 SF3B1^(K700E) isogeniccells are representative models to study the functional activity ofSF3B1 neomorphic mutations and the activity of splicing inhibitors invitro and in vivo.

Example 3: Neomorphic SF3B1 Mutations Induce Abnormal mRNA Splicing

The functional activity of neomorphic mutations found in SF3B1^(MUT)cancers was analyzed by expressing SF3B1^(WT), neomorphic SF3B1 mutants,or SF3B1^(K700R) (the mutation observed in a renal clear cell carcinomapatient that clusters with SF3B1^(WT) patients) in 293FT cells anddetermining splicing aberrations by NanoString®. The expression of allconstructs was confirmed by western blot (FIG. 7). All SF3B1 neomorphicmutations tested demonstrated the same usage of alternative splice sitesobserved in patient samples (“MUT isoform” in FIG. 8), but SF3B1^(K700R)and SF3B1^(WT) did not show aberrant splicing (FIG. 8). Moreover, theexpression of none of the SF3B1 constructs changed the overall geneexpression (“PAN-gene” in FIG. 8) or the canonical splice isoforms (“WTisoform” in FIG. 8). This indicated both a correlation between thepresence of the neomorphic SF3B1 mutations and alternative splicing aswell as similar functional activity of the different neomorphicmutations, as was indicated by the RNA-Seq analysis of patient samples.

The correlation between the SF3B1^(K700E) neomorphic mutation andaberrant splicing was analyzed using tetracycline-inducible shRNA toselectively knockdown the neomorphic SF3B1 mutant or SF3B1^(WT) allelein Panc 05.04 and Panc 10.05 cell lines (neomorphic SF3B1^(MUT) andSF3B1^(WT) cell lines, respectively; obtained from the American TypeCulture Collection [ATCC] or from RIKEN BioResource Center and culturedas instructed).

For the knockdown experiment, virus encoding shRNA was prepared inLentiX-293T cells (Clontech), which were cultured according to themanufacturer's instruction. The inducible shRNA were cloned into AgeIand EcoRI of the pLKO-iKD-H1 euro vector. The sequences of hairpinswere:

shRNA #13 SF3B1^(PAN) (SEQ ID NO: 1180) GCGAGACACACTGGTATTAAG, shRNA #8SF3B1^(WT) (SEQ ID NO: 1181) TGTGGATGAGCAGCAGAAAGT; and shRNA #96SF3B1^(MUT) (SEQ ID NO: 1182) GATGAGCAGCATGAAGTTCGG.

Cells were transfected with 2.4 μg of target pLKO-shRNA plasmid, plus2.4 μg of p Δ 8.91 (packaging), and 0.6 μg VSVG (envelope) using TransITreagent (Mirus). The virus was used to infect Panc 05.04 and Panc 10.05by spin infection using Polybrene (Millipore). The day after infection,the cells were cultured in selecting media (1.25 μg/ml Puromycin [LifeTechnologies]) for 7 days to select for shRNA-expressing cells. Theselected cells were cultured in the presence or absence of Doxycyclinehyclate (100 ng/mL; Sigma) to induce the shRNA. Cells were harvested forprotein and RNA at day 4 post-induction. In addition, cells were seededfor colony forming assay and CellTiter-Glo® assay (Promega). At day 9,cells were fixed with formaldehyde and stained with crystal violet.

To confirm SF3B1 knockdown using western blots, protein extracts wereprepared by lysing the cells with RIPA (Boston BioProducts). Twenty to25 μg of protein from each sample was separated by SDS-PAGE andtransferred to nitrocellulose membranes (iblot, Life Technologies).Membranes were first blocked with Odyssey Blocking Buffer (Li-Cor) andthen incubated with SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH(Sigma). Li-Cor donkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit800CW were used as secondary antibodies and detected by Odyssey imager(Li-Cor).

To confirm SF3B1 knockdown by allele specific qPCR, RNA was isolatedfrom the cells and retrotranscribed using MagMax for Microarray andSuperscript VILO II (Life Technologies), respectively according to themanufacturer manual. qPCR was performed using ViiA7 (Life Technologies).The reaction included 20-50 ng cDNA, Power SYBR green master mix (LifeTechnologies) and 300 nM primers. The following primers were used:

SF3B1^(WT): (SEQ ID NO: 1183) FW 5′-GACTTCCTTCTTTATTGCCCTTC and (SEQ IDNO: 1184) RW 5′-AGCACTGATGGTCCGAACTTTC, SF3B1^(MUT): (SEQ ID NO: 1185)FW 5′-GTGTGCAAAAGCAAGAAGTCC and (SEQ ID NO: 1186) RW5′-GCACTGATGGTCCGAACTTCA, SF3B1^(PAN): (SEQ ID NO: 1187) FW5′-GCTTGGCGGTGGGAAAGAGAAATTG and (SEQ ID NO: 1188) RW5′-AACCAGTCATACCACCCAAAGGTGTTG, β-actin (internal control): (SEQ ID NO:1189) FW 5′-GGCACCCAGCACAATGAAGATCAAG and (SEQ ID NO: 1190) RW5′-ACTCGTCATACTCCTGCTTGCTGATC.Biological and technical triplicates were performed.

The western blotting and allele specific PCR both confirmed knockdown ofthe SF3B1 alleles (FIGS. 9 and 10).

To determine the association between the expression of SF3B1 mutationsand aberrant splicing, RNA isolated from the cells followingdoxycycline-induced knockdown was analyzed by NanoString®. In Panc05.04, after knockdown of the neomorphic SF3B1^(MUT) allele, theaberrant splice variants were downregulated and the canonical splicevariants were upregulated, whereas the opposite was observed withselective depletion of the SF3B1^(WT) allele (FIG. 11A), indicating thatthe neomorphic SF3B1^(MUT) protein does not possess wild-type splicingactivity. The expression of a pan shRNA induced the regulation of allsplice variants as well as the depletion of SF3B1^(WT) in Panc 10.05cells (FIG. 11B). SF3B1^(PAN) knockdown impaired growth and colonyformation in both cell lines, while a minimal effect was observed withselective depletion of neomorphic SF3B1^(MUT) in Panc05.04 cells (FIGS.12 and 13). When the SF3B1^(WT) allele was knocked down in Panc 05.04cells, only a partial viability effect was observed, whereas SF3B1^(PAN)knockdown prevented colony formation and cell proliferation (FIGS. 12and 14), indicating that pan-inhibition of SF3B1 leads to antitumoractivity in vitro and in vivo.

Example 4: Modulation of Neomorphic SF3B1^(MUT) Splicing

Overall Effect of E7107 on Splicing

E7107 is a small-molecule compound that inhibits splicing by targetingthe U2 snRNP-associated complex SF3B (Kotake, Y. et al. “Splicing factorSF3b as a target of the antitumor natural product pladienolide.” NatChem Biol 3, 570-575, doi:10.1038/nchembio.2007.16 [2007]). The abilityof E7107 to inhibit splicing was observed in an in vitro splicing assay(IVS) using the substrate Ad2 (Pellizzoni, L., Kataoka, N., Charroux, B.& Dreyfuss, G. “A novel function for SMN, the spinal muscular atrophydisease gene product, in pre-mRNA splicing.” Cell 95, 615-624 [1998])and nuclear extracts from the Nalm-6 isogenic cell lines or 293F cells(Life Technologies; cultured according to the manufacturer'sinstructions) expressing Flag-tag SF3B1^(WT) or SF3B1^(K700E), asfollows.

Nuclear extracts were prepared from 293F cells transfected withpFLAG-CMV-2-SF3B1 plasmids, or from isogenic Nalm-6 cells (SBHSciences). The plasmids were generated by cloning the mxSF3B1 gene intothe HindIII and KpnI sites of pFLAG-CMV2 (Sigma), and the mutationsmxSF3B1^(K700E), mxSF3B1^(R1074H) and mxSF3B1^(K700E-R1074H) wereintroduced using the same site-directed mutagenesis kit. Cell pelletswere resuspended in hypotonic buffer (10 mM HEPES pH 7.9, 1.5 mM MgCl₂,10 mM KCl, 0.2 mM PMSF, and 0.5 mM DTT; for Nalm-6 cells, 40 mM KCl wasused). The suspension was brought up to a total of five packed cellvolumes (PCV). After centrifugation, the supernatant was discarded, andthe cells were brought up to 3 PCV with hypotonic buffer, and incubatedon ice for 10 minutes. Cells were lysed using a dounce homogenizer andthen centrifuged. The supernatant was discarded, and the pellet wasresuspended with ½ packed nuclear volume (PNV) of low salt buffer (20 mMHEPES pH 7.9, 1.5 mM MgCl₂, 20 mM KCl, 0.2 mM EDTA, 25% glycerol, 0.2 mMPMSF, 0.5 mM DTT), followed by ½ PNV of high salt buffer (same as lowsalt buffer except 1.4M KCl was used). The nuclei were gently mixed for30 minutes before centrifuging. The supernatant (nuclear extract) wasthen dialyzed into storage buffer (20 mM HEPES pH 7.9, 100 mM KCl, 0.2mM EDTA, 20% glycerol, 0.2 mM PMSF, 0.5 mM DTT). Protein concentrationwas determined using NanoDrop 8000 UV-Vis spectrophotometer (ThermoScientific).

For in vitro splicing (IVS) reactions, an Ad2-derived sequence(Pellizzoni, L., Kataoka, N., Charroux, B. & Dreyfuss, G. “A novelfunction for SMN, the spinal muscular atrophy disease gene product, inpre-mRNA splicing.” Cell 95, 615-624 [1998]) was cloned into the pGEM-3Zvector (Promega) using EcoRI and XbaI restriction sites. The resultingpGEM-3Z-Ad2 plasmid was linearized using XbaI, purified, resuspended inTE buffer, and used as a DNA template in the in vitro transcriptionreaction. The Ad2 pre-mRNA was generated and purified using MEGAScriptT7 and MegaClear kits, respectively (Invitrogen). Twenty μL splicingreactions were prepared using 80 μg nuclear extracts, 20U RNAsinRibonuclease inhibitor (Promega), 10 ng Ad2 pre-mRNA, and varyingconcentrations of E7107. After a 15 minute pre-incubation, activationbuffer (0.5 mM ATP, 20 mM creatine phosphate, 1.6 mM MgCl₂) was added toinitiate splicing, and the reactions were incubated for 90 minutes. RNAwas extracted using a modified protocol from a RNeasy 96 Kit (Qiagen).The splicing reactions were quenched in 350 μL Buffer RLT Plus (Qiagen),and 1.5 volume ethanol was added. The mixture was transferred to anRNeasy 96 plate, and the samples were processed as described in the kitprotocol. RNA was diluted 1/10 with dH₂O. 10 μL RT-qPCR reactions wereprepared using TaqMan RNA-to-C_(T) 1-step kit (Life Technologies), 8.5μL RNA, and 1 μL of Ad2 mRNA primers/probe set (FW 5′ACTCTCTTCCGCATCGCTGT (SEQ ID NO: 1191), RW 5′-CCGACGGGTTTCCGATCCAA (SEQID NO: 1192) and probe 5′ CTGTTGGGCTCGCGGTTG (SEQ ID NO: 1193)).

To evaluate pSF3B1, in vitro splicing reactions were prepared asdescribed above. To quench the reactions, 6× Laemmli Buffer (BostonBioproducts) was added, and the samples were subjected to SDS-PAGE gels(Life Technologies). The separated proteins were transferred ontonitrocellulose membranes then blocked with blocking buffer (50% OdysseyBlocking Buffer (Li-Cor Biosciences) and 50% TBST). The blots wereincubated with anti-SF3B1 antibody overnight, after several washes inTBST, they were incubated with IRDye 680LT donkey-α-mouse-IgG antibodyand visualized using an Odyssey CLx imaging system (Li-Cor Biosciences).

E7107 was able to inhibit splicing in nuclear extracts from both theNalm-6 cells or the 293F cells expressing Flag-tag SF3B1^(WT) orSF3B1^(K700E) (FIGS. 15A and 15B).

E7107 Binds Both SF3B1^(WT) and SF3B1^(K700E) Proteins

The ability of E7107 to bind both SF3B1^(WT) and SF3B1^(K700E) proteinswas evaluated in a competitive binding assay using Flag-tag SF3B1proteins immunoprecipitated with anti-Flag antibody from transientlytransfected 293F cells. Batch immobilization of antibody to beads wasprepared by incubating 80 μg of anti-SF3B1 antibody (MBL International)and 24 mg anti-mouse PVT SPA scintillation beads (PerkinElmer) for 30minutes. After centrifugation, the antibody-bead mixture was resuspendedin PBS supplemented with PhosSTOP phosphatase inhibitor cocktail (Roche)and complete ULTRA protease inhibitor cocktail (Roche). Nuclear extractswere prepared by diluting 40 mg into a total volume of 16 mL PBS withphosphatase and protease inhibitors, and the mixture was centrifuged.The supernatant was transferred into a clean tube, and the antibody-beadmixture was added and incubated for two hours. The beads were collectedby centrifuging, washed twice with PBS+0.1% Triton X-100, andresuspended with 4.8 mL of PBS. 100 μL binding reactions were preparedusing slurry and varying concentrations of E7107. After 15 minutespre-incubation at room temperature, one nM ³H-probe molecule (describedin Kotake, Y. et al. Splicing factor SF3b as a target of the antitumornatural product pladienolide. Nat Chem Biol 3, 570-575,doi:10.1038/nchembio.2007.16 [2007]) was added. The mixture wasincubated at room temperature for 15 minutes, and luminescence signalswere read using a MicroBeta2 Plate Counter (PerkinElmer).

As shown in FIG. 16A, E7107 was able to competitively inhibit binding ofthe ³H-probe molecule in a similar manner to either SF3B1^(WT) (IC₅₀: 13nM) or SF3B1^(K700E) (IC₅₀: 11 nM).

Effect of E7107 and Other Compounds on Normal and Aberrant Splicing

E7107 was also tested in vitro in Nalm-6 isogenic cell lines for theability to modulate normal and aberrant splicing induced by SF3B1^(WT)and SF3B1^(K700E) protein. Nalm-6 isogenic cells were treated withincreasing concentrations of E7107 for six hours and RNA was analyzed byqPCR. As shown in FIG. 16B, canonical splicing was observed, withaccumulation of pre-mRNA for EIF4A1 and downregulation of the maturemRNA SLC25A19 observed in both cell lines. Additionally, downregulationof mature mRNA of the two abnormally spliced isoforms of COASY andZDHHC16 was observed in Nalm-6 SF3B1^(K700E) (FIG. 16B).

To investigate the broader activity of E7107 on normal and aberrantsplicing, RNA from Nalm-6 isogenic cells treated for two and six hoursat 15 nM was analyzed by NanoString®. Only partial inhibition ofsplicing was observed at two hours in both isogenic cell lines, and atthe level of gene, WT-associated isoforms, and MUT-associated isoformexpression. After six hours of treatment, clear inhibition was detectedfor all isoforms quantified (FIG. 17). Similar results were obtained byRNA-Seq analysis of isogenic cell lines treated for six hours with E7107at 15 nM (FIG. 18). Normal and aberrant splicing in the isogenic celllines was also analyzed by RNA-Seq following treatment with one ofadditional compounds having formulas 1 or 2. Like E7107, each of theseadditional compounds inhibited expression of both WT-associated andMUT-associated RNA isoforms (FIG. 19; compound is indicated by formulanumber above each vertical pair of graphs). For the RNA-Seq analysis,cells were washed with PBS after treatment with E7107 or other testcompound, and RNA was isolated using PureLink (Life Technology) asreported in the manufacturer's manual. cDNA library preparation,sequencing and raw read filtering was performed as described in Ren, S.et al. “RNA-Seq analysis of prostate cancer in the Chinese populationidentifies recurrent gene fusions, cancer-associated long noncoding RNAsand aberrant alternative splicings.” Cell Res 22, 806-821,doi:10.1038/cr.2012.30 (2012).

In addition, the ability of E7107 to modulate splicing was tested inmice bearing human tumor xenografts. Nalm-6 isogenic xenograft mice weregenerated by subcutaneously implanting 10×10⁶ Nalm-6 isogenic cells intothe flank of CB17-SCID mice, and tumors from these mice were collectedat different timepoints after a single intravenous (IV) dose of E7107 (5mg/kg) and analyzed to determine compound concentrations and splicingregulation. RNA was isolated from the tumors using RiboPure™ RNApurification kit (Ambion®) and used for NanoString® assay or qPCR. TheRNA was retrotranscribed according to the instructions of theSuperScript® VILO™ cDNA synthesis kit (Invitrogen™) and 0.04 μl of cDNAwas used for qPCR. qPCR for pre-mRNA EIF4A1 and mature mRNA SLC24A19 andpharmacokinetic evaluation were performed as described in Eskens, F. A.et al. “Phase I pharmacokinetic and pharmacodynamic study of thefirst-in-class spliceosome inhibitor E7107 in patients with advancedsolid tumors.” Clin Cancer Res 19, 6296-6304,doi:10.1158/1078-0432.CCR-13-0485 (2013). The primers and probes usedfor ZDHHC16 were the following: FW 5′-TCTTGTCTACCTCTGGTTCCT (SEQ ID NO:1194), RW 5′ CCTTCTTGTTGATGTGCCTTTC (SEQ ID NO: 1195) and probe 5′ FAMCAGTCTTCGCCCCTCTTTTCTTAG (SEQ ID NO: 1196). The primers and probes usedfor COASY were the following: FW 5′-CGGTGGTGCAAGTGGAA (SEQ ID NO: 1197),RW 5′-GCCTTGGTGTCCTCATTTCT (SEQ ID NO: 1198) and probe5′-FAM-CTTGAGGTTTCATTTCCCCCTCCC (SEQ ID NO: 1199). E7107 reached similardrug concentrations and modulated canonical splicing (accumulation ofpre-mRNA for EIF4A1 and downregulation of the mature mRNA SLC25A19) inboth Nalm-6 SF3B1^(K700K) and Nalm-6 SF3B1^(K700E) models anddownregulated abnormal splicing of COASY and ZDHHC16 in the Nalm-6SF3B1^(K700E) cells (FIG. 20), as observed in vitro. The canonical andaberrant splice mRNA isoforms were downregulated by E7107 as early asone hour following administration of the compound, and expressionnormalized shortly after treatment (FIG. 21), consistent with E7107pharmacokinetic profile. Similar results were observed in a Panc 05.04neomorphic SF3B1 xenograft model (FIG. 22). All these data indicate thatE7107 is a pan-splicing modulator that can bind and inhibit SF3B1^(WT)and SF3B1^(K700E) proteins in vitro and in vivo.

Example 5: E7107 has Anti-Tumor Activity Via SF3B1 Modulation

SF3B1 modulator E7107 was tested for antitumor activity in vivo bydetermining the effect of E7107 in a subcutaneous model of Nalm-6SF3B1^(K700E). 10×10⁶ Nalm-6 SF3B1^(K700E) were subcutaneously implantedinto the flank of CB17-SCID mice, and mice were administered E7107intravenously once a day for 5 consecutive days (QD×5) at three welltolerated dose levels (1.25, 2.5 and 5 mg/kg). After this dosing, theanimals were monitored until they reached either of the followingendpoints: 1) excessive tumor volume measured three times a week (tumorvolume calculated by using the ellipsoid formula: (length×width)/2), or2) development of any health problem such as paralysis or excessive bodyweight loss. Partial regression (PR) and complete regression (CR) aredefined as 3 consecutive tumor measurements <50% and <30% of startingvolume respectively.

In the 1.25 mg/kg group, all animals (n=10) reached complete regression(CR) in the Nalm-6 SF3B1^(K700E) xenograft group. In the 2.5 mg/kggroup, 10/10 CRs were observed in the Nalm-6 SF3B1^(K700E) group by day9. In the 5 mg/kg group all Nalm-6 SF3B1^(K700E) xenograft animalsreached CR as early as 9 days post treatment and had mean survival timesof over 250 days (FIGS. 23 and 24). These data demonstrate antitumoractivity of SF3B1 modulator in SF3B1^(K700E) xenografts in vivo.

The ability of E7107 to inhibit splicing in CLL patient samples in vitrowas determined by isolating RNA from samples of E7107-treated patientcells treated for 6 hours with E7107 at 10 nM and performing RNA-Seqanalysis. To do so, cells were washed with PBS after treatment withE7107, and RNA was isolated using PureLink (Life Technology) as reportedin the manufacturer's manual. cDNA library preparation, sequencing andraw read filtering was performed as described in Ren, S. et al. “RNA-Seqanalysis of prostate cancer in the Chinese population identifiesrecurrent gene fusions, cancer-associated long noncoding RNAs andaberrant alternative splicings.” Cell Res 22, 806-821,doi:10.1038/cr.2012.30 (2012). As shown in FIG. 25, E7107 inhibited theexpression of canonical splice isoforms in SF3B1^(WT) and neomorphicSF3B1^(MUT) patient samples. E7107 was able to modulate aberrantsplicing in all CLL patient samples carrying neomorphic SF3B1 mutations.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the following claims.

The invention claimed is:
 1. A method of treating a patient having a neoplastic disorder, comprising administering an SF3B1-modulating compound to the patient, wherein a sample from the patient has been tested to detect expression of five splice variants comprising SEQ ID NO:41, SEQ ID NO:61, SEQ ID NO:101, SEQ ID NO:160, and SEQ ID NO:230, and the sample expresses the five splice variants.
 2. The method of claim 1, wherein the sample expresses at least one additional splice variant.
 3. The method of claim 1, wherein the sample comprises one or more cells, blood or a blood fraction, and/or a tissue biopsy.
 4. The method of claim 1, wherein the sample is from a hematological cancer or a solid tumor.
 5. The method of claim 4, wherein the hematological cancer is selected from chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, acute monocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, and multiple myeloma; and/or the solid tumor is selected from breast cancer, lung cancer, liver cancer, prostate cancer, pancreatic cancer, colon cancer, colorectal cancer, skin cancer, ovarian cancer, uterine cancer, cervical cancer, and renal cancer.
 6. The method of claim 1, wherein the SF3B1-modulating compound comprises a pladienolide or a pladienolide analog.
 7. The method of claim 6, wherein the pladienolide analog is selected from pladienolide B, pladienolide D, E7107, a compound of formula 1:

a compound of formula 2:

a compound of formula 3:

and a compound of formula 4:


8. The method of claim 1, wherein the SF3B1-modulating compound comprises a compound of formula 2:


9. A method of treating a patient having a neoplastic disorder, comprising: a) detecting expression of five splice variants comprising SEQ ID NO:41, SEQ ID NO:61, SEQ ID NO:101, SEQ ID NO:160, and SEQ ID NO:230 in a sample from the patient; and b) administering an SF3B1-modulating compound to the patient.
 10. The method of claim 9, wherein detecting expression of the five splice variants comprises contacting the sample with one or more nucleic acid probes capable of specifically hybridizing to the five splice variants; and detecting binding of the one or more nucleic acid probes to the five splice variants.
 11. The method of claim 10, wherein the one or more nucleic acid probes comprise a label and/or a molecular barcode.
 12. The method of claim 9, wherein the sample expresses at least one additional splice variant.
 13. The method of claim 9, wherein the sample comprises one or more cells, blood or a blood fraction, and/or a tissue biopsy.
 14. The method of claim 9, wherein the sample is from a hematological cancer or a solid tumor.
 15. The method of claim 14, wherein the hematological cancer is selected from chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, acute monocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, and multiple myeloma; and/or the solid tumor is selected from breast cancer, lung cancer, liver cancer, prostate cancer, pancreatic cancer, colon cancer, colorectal cancer, skin cancer, ovarian cancer, uterine cancer, cervical cancer, and renal cancer.
 16. The method of claim 9, wherein the SF3B1-modulating compound comprises a pladienolide or a pladienolide analog.
 17. The method of claim 16, wherein the pladienolide analog is selected from pladienolide B, pladienolide D, E7107, a compound of formula 1:

a compound of formula 2:

a compound of formula 3:

and a compound of formula 4:


18. The method of claim 9, wherein the SF3B1-modulating compound comprises a compound of formula 2: 